European Journal of Medical Research

Research progress of metabolomics in cervical cancer

Abstract Introduction Cervical cancer threatens women's health seriously. In recent years, the incidence of cervical cancer is on the rise, and the age of onset tends to be younger. Prevention, early diagnosis and specific treatment have become the main means to change the prognosis of cervical cancer patients. Metabolomics research can directly reflect the changes of biochemical processes and microenvironment in the body, which can provide a comprehensive understanding of the changes of metabolites in the process of disease occurrence and development, and provide new ways for the prevention and diagnosis of diseases. Objectives The aim of this study is to review the metabolic changes in cervical cancer and the application of metabolomics in the diagnosis and treatment. Methods PubMed, Web of Science, Embase and Scopus electronic databases were systematically searched for relevant studies published up to 2022. Results With the emergence of metabolomics, metabolic regulation and cancer research are further becoming a focus of attention. By directly reflecting the changes in the microenvironment of the body, metabolomics research can provide a comprehensive understanding of the patterns of metabolites in the occurrence and development of diseases, thus providing new ideas for disease prevention and diagnosis. Conclusion With the continuous, in-depth research on metabolomics research technology, it will bring more benefits in the screening, diagnosis and treatment of cervical cancer with its advantages of holistic and dynamic nature.

Long non-coding RNA H19 promotes cervical cancer development via targeting the microRNA-140/ALDH1A1 axis

Dysregulation of long non-coding RNA H19 (lncRNA H19) is involved in cervical cancer (CC) progression. This study aims to unveil the specific role and relevant mechanism of lncRNA H19 in CC. The expression of lncRNA H19 in CC cells was detected by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). CC cells were transfected with sh-H19, followed by cell proliferation, apoptosis, migration and invasion were examined. After location of H19 in cells using fluorescence in Situ Hybridization (FISH), target microRNAs (miRNAs) and genes associated with lncRNA H19 were predicted using bioinformatics analysis and validated by dual-luciferase reporter assay. Finally, the specific role of lncRNA H19 in CC was explored in vivo. The upregulation of lncRNA H19 was observed in CC cells. LncRNA H19 knockdown inhibited the proliferation, migration, and invasion of CC cells, and remarkably promoted CC cell apoptosis. LncRNA H19 was localized in the nucleus and interacted with miR-140 that was downregulated in CC cells. MiR-140 inhibition reversed the effects of lncRNA H19 knockdown on CC cell development. MiR-140 targets ALDH1A1, and lncRNA H19 knockdown decreased the ALDH1A1 expression, which was rescued by miR-140 inhibition. In vivo experiments also shown that reduction of lncRNA H19 diminishes tumor growth via targeting the miR-140/ALDH1A1 axis. LncRNA H19 promotes the malignant progression of CC through targeting miR-140/ALDH1A1 axis.

Development and validation of a nomogram for predicting overall and cancer-specific survival in elderly patients (≥ 65 years) with epithelial ovarian cancer

Current evidence indicates an uptick in both morbidity and mortality rates of epithelial ovarian cancer (EOC) among the elderly (65 year and older) over the past few years. To date, standardized treatment for elderly patients remains undeveloped. This study utilizes the Surveillance, Epidemiology, and End Results (SEER) database to extract relevant clinicopathological data and construct two nomograms aimed at predicting the prognosis of elderly (65 year and older) patients with EOC. This objective is intended to assist clinicians during clinical decision-making and to assist in individualized prognostication and support clinical decision-making of elderly (65 year and older) EOC patient. Our analysis screened a total of 22,181 eligible patients, randomly divided into a training cohort (n = 15,529) and validation cohort (n = 6652) at a ratio of 7:3. 64 cases over 65 year old EOC patient were collected for external validation in our hospital. COX and LASSO analyses were used to screen the independent risk factors for overall survival (OS) and cancer-specific survival (CSS) in elderly patients with EOC. The independent risk factors were used to establish a nomogram by using the "rms" package. The predictive and clinical utility of nomograms was assessed using concordance index, area under the curve (AUC), calibration curve, decision curve analysis and external validation. Kaplan-Meier analysis was conducted to further stratify OS and CSS in high and low-risk groups, assessing the nomograms' stratification efficacy. The AUCs of the training and validation cohort for OS and CSS prediction at 0.5, 1, 3, 5, and 10 years were significantly higher than the American Joint Committee on Cancer (AJCC) staging system (8th edition). Time-dependent AUC analysis from 1 to 10 years confirmed the nomograms' predictive superiority over the AJCC staging system for both OS and CSS in the training and validation cohorts. Compared with the age, AJCC staging system, the DCA curves of the nomogram showed a greater net gain in the training and external validation cohorts. In the external validation group, C-index of nomogram was 0.938 [95% CI 0.888-0.988], which was significantly better than that of stage (0.762) [95% CI 0.693-0.832] and the results showed that the AUC of Nomogram was significantly higher than that of stage at 1, 3, and 5-year OS and CSS. KM analysis showed that the prognosis of the low-risk group was significantly higher than that of the high-risk group. The developed nomograms outperformed the AJCC staging system in predicting both OS and CSS in elderly (65 year and older) EOC patient. The developed nomograms offer an effective method for predicting the OS and CSS of elderly ovarian cancer patients, aiding clinicians in making personalized survival projections and refining treatment recommendations.

Research on the inhibitory effect of hydrogen gas on ovarian cancer and potential mechanisms

Ovarian cancer is one of the most fatal malignancies in women worldwide; current treatment approaches still struggle to effectively control tumor progression. Therefore, it is imperative to explore novel and more effective therapeutic approaches. Hydrogen shows promise as a novel adjuvant therapy, offering new perspectives for ovarian cancer treatment. This study primarily investigates the effects of hydrogen on SKOV3 ovarian cancer cell line viability, apoptosis, migration, invasion, MDA, SOD levels, and key regulatory proteins through experiments including CCK-8, flow cytometry, scratch assay, Transwell assay, immunofluorescence, Western blot, and ELISA. HE staining, TUNEL, immunohistochemistry, immunofluorescence, Western blot, and ELISA were used to verify the antitumor effects of hydrogen in vivo. The results showed that hydrogen inhibited cell viability, migration, and invasion, promoted apoptosis, and induced G1/G2 phase arrest in SKOV3 cells. Additionally, hydrogen promoted ROS production, downregulated the expression of HIF-1α, NF-κB p65, and P-p65 proteins, decreased SOD levels, and increased MDA levels. The results of animal experiments showed that the tumor weight and volume in the hydrogen group were significantly smaller than those in the control group. At the same time, hydrogen promoted tumor cell apoptosis, reduced the levels of angiogenesis markers within the tumor, lowered the protein levels of HIF-1α and p65, increased MDA levels, and decreased SOD levels. Hydrogen provides a new approach for the treatment of ovarian cancer.

Identification of neoantigen epitopes in cervical cancer by multi-omics analysis

Tumor vaccines enhance the immune response and cytotoxicity of tumor-specific T cells and show promising clinical therapeutic efficacy. Although most cervical cancer cells express HPV-related oncoproteins, some do not. Additionally, neoantigens worth attracting attention for cervical cancer (CC) may hold the potential for breakthroughs in the development of cervical cancer vaccines. A comprehensive computational analysis was conducted based on the tumor genome, transcriptome, and proteome data from 284 cervical cancer samples obtained from the TCGA database. Frequently mutated genes were identified. The levels of immune cell infiltration were analyzed using RNA-seq data, high-frequency mutated genes were identified as candidate genes that were significantly related to immune infiltration. Focusing on MHC class I epitopes recognized by CD8 + T cells, we predicted potential neoantigen peptides using the NetMHCpan-4.0 and NetCTL-1.2 algorithms. To further confirm the immunogenicity of the synthesized peptides, we performed flow cytometry and real-time PCR in vivo to examine markers of T cell activation and cytotoxicity. We also stimulated PBMC from patients with the corresponding HLA type with the synthesized peptides using an ELISpot assay. We identified 30 highly mutated genes, among which TTN, PRKDC, PCLO, MUC17, HUWE1, RYR2, and CREBBP positively correlated with immune cell infiltration into the tumor microenvironment. PCLO exhibited higher protein expression in tumor tissues than in the corresponding normal tissues, making it a potential tumor antigen. The PCLO peptides SISRFTLEK and LSEAGHFFY exhibited the highest predicted scores among the cancer antigens and strong immunogenicity in vivo. Our analysis highlights the potential of PCLO as a candidate gene for enhancing immune cell infiltration and activating immune responses in tumors. The peptides SISRFTLEK (PCLO

Identification of immune-related cervical cancer prognostic biomarkers and construction of prognostic model based on tumor microenvironment

Tumor microenvironment (TME) and the expression of immune-related genes (IRGs) are closely related to the development of cervical cancer (CC). This study aims to explore some IRGs as prognostic biomarkers for CC patients based on TME. The abundance of tumor-infiltrating immune cells in CC samples was assessed using single-sample gene set enrichment analysis (ssGSEA). Thus, two immune-related groups are generated according to the immune status. The differentially expressed genes were discovered based on the grouping. Then, univariate Cox and LASSO regression analyses were performed using the R package glmnet. Five IRG prognostic signatures (HLA-DMA, DMBT1, CXCR6, CX3CL1, and SEMA3A) were established after that. The protein expression of some genes was verified by immunohistochemistry (IHC). The signature of the five IRGs was identified to be an independent prognostic indicator for the overall survival in CC patients. A prognostic risk model was also constructed. CC patients were classified into high- and low-risk groups based on the median risk score. The survival time of patients in the high-risk group was shorter than that of those in the low-risk group. The five genes remarkably related to prognosis were screened, among which HLA-DMA, CXCR6, and CX3CL1 were the protective factors, whereas DMBT1 and SEMA3A were the risk factors. GO and KEGG enrichment analyses showed that the biomarkers of the five IRGs were enriched in the receptor-ligand interaction and chemokine signaling pathway. Moreover, CXCR6 expression was significantly correlated with immune cell infiltration among the five hub genes. IHC results demonstrated that the expression of SEMA3A protein level was increased, and CX3CL1 protein level was decreased in cervical cancer tissue. Immune-related prognostic biomarkers in CC include HLA-DMA, DMBT1, CXCR6, CX3CL1, and SEMA3A. The risk score for the five genes is more accurate than that for other clinical risk factors in predicting prognosis at 3 and 5 years. The higher the risk score is, the worse the prognosis of CC patients is. Five prognostic biomarkers may participate in regulating TME through chemokine-mediated signaling pathways and receptor-ligand interactions. These findings provide new insights into the immunotherapy of CC.

Chromosomal instability: a key driver in glioma pathogenesis and progression

AbstractChromosomal instability (CIN) is a pivotal factor in gliomas, contributing to their complexity, progression, and therapeutic challenges. CIN, characterized by frequent genomic alterations during mitosis, leads to genetic abnormalities and impacts cellular functions. This instability results from various factors, including replication errors and toxic compounds. While CIN’s role is well documented in cancers like ovarian cancer, its implications for gliomas are increasingly recognized. CIN influences glioma progression by affecting key oncological pathways, such as tumor suppressor genes (e.g., TP53), oncogenes (e.g., EGFR), and DNA repair mechanisms. It drives tumor evolution, promotes inflammatory signaling, and affects immune interactions, potentially leading to poor clinical outcomes and treatment resistance. This review examines CIN’s impact on gliomas through a narrative approach, analyzing data from PubMed/Medline, EMBASE, the Cochrane Library, and Scopus. It highlights CIN’s role across glioma subtypes, from adult glioblastomas and astrocytomas to pediatric oligodendrogliomas and astrocytomas. Key findings include CIN’s effect on tumor heterogeneity and its potential as a biomarker for early detection and monitoring. Emerging therapies targeting CIN, such as those modulating tumor mutation burden and DNA damage response pathways, show promise but face challenges. The review underscores the need for integrated therapeutic strategies and improved bioinformatics tools like CINdex to advance understanding and treatment of gliomas. Future research should focus on combining CIN-targeted therapies with immune modulation and personalized medicine to enhance patient outcomes.

Bone marrow toxicity in patients with locally advanced cervical cancer undergoing multimodal treatment with VMAT/IMRT: are there dosimetric predictors for toxicity?

Abstract Purpose For women with locoregionally advanced cervical cancer, the standard of care treatment is the curatively intended chemoradiation therapy (CRT). A relationship between bone marrow (BM) dose–volume histograms (DVHs) and acute hematological toxicity (HT) has been debated recently. Aim of this study was the evaluation of BM dose constraints and HT in a contemporary patient cohort. Methods Radiation treatment plans of 31 patients with cervical cancer (FIGO stage IIB–IVB) treated with intensity-modulated radiotherapy and simultaneous chemotherapy were explored retrospective. Pelvic bones (PB) and femoral heads (FH) were contoured and DVHs were correlated with white blood cells (WBC), hemoglobin levels and platelets. Results Comparing the absolute blood levels with the dose volumes of both FH and PB the data showed a significant correlation between WBC and the median dose of the FH and the median dose, V30Gy, V40Gy and V50Gy of the PB. A correlation between the toxicity grade of anemia and mean dose, maximum dose and V5Gy of the PB was found. Counting the highest grade of HT of all three blood levels of each patient, significant correlations were found for the mean and median dose, V30Gy, V40Gy and V50Gy of the PB. Conclusion The results show that blood levels may correlate with distinct dosimetric subvolumes of critical bone marrow compartments with a potential impact on therapeutic outcome and treatment-related toxicity. The data presented are in line with the previous findings on the relevance of dosimetric exposure of pelvic bony subvolumes.

ER-positive and BRCA2-mutated breast cancer: a literature review

AbstractBRCA2-mutated carriers have a high lifetime risk of breast cancer (BC), an early age of onset, and an increased risk of other cancers (including ovarian, pancreatic, and prostate cancer). Almost 70–80% of BRCA2-mutated BC are estrogen receptor (ER)-positive, which is a particular type of ER-positive BC that differs from sporadic ER-positive BC. This article reviews the clinicopathological features, treatment, and prognosis of ER-positive and BRCA2-mutated BC to provide a reference for clinical decision-making.

Evaluation of self-sampling-based cervical cancer screening strategy using HPV Selfy CE-IVD test coupled with home-collection kit: a clinical study in Italy

Abstract Background Primary human papillomaviruses (HPV) cervical cancer screening can be strengthened by offering home-collection of biological specimen as a valuable option to increase screening coverage. As recommended by World Health Organization (WHO), screening programs should consider whether the inclusion of HPV self-sampling as a complementary option within their existing screening algorithms could address the gaps in current coverage. However, few HPV screening tests are validated for self-sampling according to international guidelines. This study aimed to test a self-sampling-based screening strategy, complementary to the main screening program based on clinician-collected cervical samples. The study took place in Trieste, Italy, and it aimed to evaluate the feasibility of self-testing at home under an opt-in system during COVID-19 pandemic in order to exploit self-sampling to reduce the screening delay generated by the lockdown. Methods 500 women, who should have received the screening call in 2020, were asked, via phone call, to participate in the study. To whom agreed, a home-collection kit, including a vaginal dry swab for specimen collection, was sent. The recipients performed the sample self-collection and sent back the swab through traditional mail using a prepaid envelope. Once received by the hospital, the samples were analyzed with HPV Selfy (Ulisse BioMed, Italy), a CE-IVD HPV screening test specifically validated for self-collection. Results were further compared using cobas® 4800 HPV (Roche, Switzerland). Results 80% women sent back their swab, showing one of the highest return rate obtained in comparable studies. 34 HPV-positive women were followed up and underwent the Pap test, that revealed 8 low squamous intraepithelial lesions (LSIL) cases, later triaged to colposcopy. HPV Selfy was confirmed to be an adequate test for self-sampling-based screening. Conclusions This study further confirmed the feasibility of self-test at home screening strategy based on self-sampling with an opt-in system as a support method to enhance cervical cancer screening coverage in Italy. Enrolled women showed a high appreciation for this approach. HPV Selfy test demonstrated to be a valuable assay for cervical cancer screening based on home self-collection. Trial registration: ASUGI Trieste n. 16008/2018 and amendment 02-11/09/2020.

SENP5 promotes endometrial cancer cell growth by regulating β-catenin deSUMOylation to enhance GPX4-resistance to ferroptosis

Endometrial cancer (EC) is a significant and serious gynecological cancer, constituting a considerable risk to women's health. The desumoylation of SUMO specific peptidase 5 (SENP5) is intricately linked with various cancers. Nonetheless, the function of SENP5 in EC and its regulation of EC progression through the related mechanism of desumoylation modification remain elusive. Five samples of EC tumor tissues, along with para-cancerous tissues, were obtained. The expression of SENP5 in EC was assessed using reverse transcription-polymerase chain reaction (RT-qPCR), immunohistochemistry (IHC), and Western blot. HEC-1-B cells were treated with liposomes to interfere SENP5 and/or β-catenin expression. The methodologies employed to assess the impact of SENP5 on the proliferation of EC cells via β-catenin included RT-qPCR, Western blot, CCK8, EDU, and C11-BODIPY methods. Western blot, co-immunoprecipitation (CO-IP), and SUMOylation analysis were conducted to investigate the desumoylation modification of β-catenin by SENP5. SENP5 exhibited elevated expression levels in EC cancer tissues and was correlated with a negative prognosis for patients diagnosed with EC. The suppression of SENP5 inhibited the expression of β-catenin and GPX4, activated ferroptosis, and inhibited HEC-1-B -cell proliferation. Knockdown of β-catenin counteracted the impact of SENP5 overexpression on ferroptosis and HEC-1-B proliferation. In addition, SENP5 stabilized β-catenin level in HEC-1-B cells through desumoylation modification of the β-catenin protein. SENP5 promotes GPX4-mediated ferroptosis resistance, thereby enhancing the proliferation of EC cells by regulating β-catenin desumoylation, this finding indicates that SENP5 may serve as a promising target for therapeutic interventions in the treatment of EC.

Development of a novel prognostic model based on laminin α5, associated with immune infiltration and therapeutic response in ovarian cancer utilizing online resources

Ovarian cancer (OC) is one of the most pervasive malignancies in women and is recognized for its high recurrence and metastasis rates, resulting in a poor prognosis. Regrettably, reliable indicators for the timely detection and prognosis of OC are currently insufficient. Our research aimed to evaluate the immune therapeutic and prognostic possibilities of laminin α5 (LAMA5) in OC using bioinformatics analysis. LAMA5 expression and clinical features were analyzed in OC tissues using TCGA and GEO databases. Cox and LASSO analyzes were utilized for the identification of genes with differential expression, leading to the development of a prognostic model centered around LAMA5. Time-based receiver operating characteristic curves were examined to assess the nomogram's accuracy. Furthermore, we explored the correlation between risk score and tumor mutational burden (TMB), infiltration of immune cells, immune response, and chemotherapy. A signaling pathway analysis was performed to determine the associations between our findings. Immunohistochemical (IHC) analysis was conducted to validate the prognostic significance of LAMA5. Our study demonstrated that LAMA5 was overexpressed in OC patients. According to the Kaplan-Meier survival analysis, the patients with low LAMA5 expression exhibited a significantly higher survival rate compared to those with high LAMA5 expression, indicating a negative impact on the overall prognosis. Additionally, LAMA5 can serve as a distinct prognostic determinant. We developed a sophisticated predictive model that integrated six genes with distinct expression patterns. A clear correlation was found between the predictive model and TMB, immune cell infiltration, as well as the efficacy of immunotherapy and chemotherapy. IHC revealed that LAMA5 protein expression was significantly increased in OC tissues. An increased expression of LAMA5 was associated with an unfavourable outcome in relation to OS and PFS in patients. This study offers novel perspectives on immunotherapy for OC by demonstrating the reliability of a prognostic model based on LAMA5 in predicting patient outcomes. Our risk model holds promise as an efficient biomarker for enhancing prognostic prediction accuracy and facilitating personalized treatment strategies for OC patients.

A chemokine-based prognostic model featuring CXCL8, ITGA5, BACE2, CCR7, CERS4, and MEI1 for cervical cancer

Cervical cancer, often caused by persistent high-risk HPV infection, remains a significant public health challenge with limited treatment options. Chemokines play crucial roles in immune cell recruitment and tumor microenvironment modulation. This study proposes a chemokine-based predictive model to optimize personalized treatment and prognosis. Bulk RNA-seq and clinical data from TCGA-CESC and GSE52903 cohorts were analyzed along with 152 chemokine-related genes (CRGs). Prognostic CRGs were identified via Cox regression, consensus clustering was used for subtypes. Differentially expressed genes (DEGs) were analyzed with "limma". Then, a RiskScore model was developed through Lasso algorithm, and ROC curves were performed for the model performance. CIBERSORT, TIMER, MCP-counter and TIDE were used for the immune differences. Drug sensitivity was analyzed via IMvigor210 cohort and the "oncoPredict" package. GSEA identified enriched pathways, and single-cell RNA-seq (GSE168652) explored the special cell types in tumor and normal tissues. Finally, we examined the model gene expression by qPCR, and cell proliferation, migration and invasion through CCK-8, wound healing and trans-well assay. Through the analysis of the TCGA-CESC and GSE52903 cohorts, we first identified 39 prognostic CRGs and subsequently stratified cervical cancer patients into two molecular subtypes (C1/C2) based on their expression profiles. These subtypes exhibited significant differences in overall survival (C1 with a more favorable prognosis than C2) and distinct immune infiltration patterns. We then developed and validated a robust risk score model based on subtype-specific differentially expressed genes, which incorporated six genes (CXCL8, ITGA5, BACE2, CCR7, CERS4, and MEI1). Furthermore, the risk score revealed profound heterogeneity in the tumor immune microenvironment: the low-risk group was characterized by enhanced infiltration of immune cells (e.g., CD8 + T cells, activated CD4 + T cells, and M1 macrophages) and a higher predicted response to immunotherapy, whereas the high-risk group was associated with an immunosuppressive phenotype and T cell dysfunction. Mechanistically, the high-risk signature was linked to the activation of pro-tumorigenic pathways, including focal adhesion, ECM-receptor interaction, and the IL-17 signaling pathway. Single-cell transcriptomic analysis further pinpointed the cellular origins of key model genes, revealing that CXCL8 was predominantly highly expressed in tumor-associated monocytes/macrophages. Finally, in vitro functional assays confirmed that CXCL8 was significantly upregulated in cervical cancer cells, and its knockdown potently suppressed cell proliferation, migration, and invasion. This study identified a distinct chemokine-driven molecular classification and constructed a chemokine-related prognostic model for cervical cancer. These findings offer novel insights into tumor immunobiology and provide a promising tool for improving individualized risk stratification and therapeutic strategies for cervical cancer.

High-risk factors and predictive models for hemorrhagic chronic radiation proctitis

Hemorrhagic chronic radiation proctitis (CRP) is a common and challenging complication after pelvic radiation therapy. Identifying high-risk factors, predicting its occurrence, and optimizing radiotherapy plans are key to preventing hemorrhagic CRP. This study retrospectively examined potential risk factors and developed a nomogram to predict its onset. This retrospective study included cervical carcinoma patients who received pelvic radiotherapy at Chongqing University Cancer Hospital from March 2014 to December 2021. Hemorrhagic CRP was diagnosed by colonoscopy. Logistic regression identified factors for a nomogram model, which was evaluated using ROC curve, calibration curve, and decision curve analysis. Among 221 patients, 125 were diagnosed with hemorrhagic CRP, occurring at a median of 14.45 months after pelvic radiotherapy. Age (≥ 54 years), weight (< 52 kg), and radiation dose (≥ 72 Gy) were identified as risk factors. A nomogram was developed, with AUC values of 0.741 and 0.74 in the training and validation cohorts. Decision and clinical impact curves showed the model's benefit over a probability range of 0.25 to 0.85 in both sets. In this study, we constructed and developed a nomogram for predicting hemorrhagic CRP risk. The good results in calibration curves, ROC curve analysis, and decision curves indicated that the nomogram had promise for clinical application. It may serve as a reference for radiologists in designing radiotherapy plan to help mitigate the risk of hemorrhagic CRP.

Age at menarche is inversely related to the prevalence of uterine cancer

Abstract Objectives The objective of this study was to investigate the relationship between the age of menarche and the prevalence of malignancies of the uterus and ovaries. Methods A total of 5540 women were screened from those who participated in the National Health And Nutrition Examination Survey (NHANES) questionnaire from 2007 to 2020, and their variable factors of age, race, education level, Poverty Impact Ratio (PIR), marital status, Body Mass Index (BMI), waist circumference, duration of moderate exercise, smoking habits, hypertension status, energy intake, diabetes and alcohol consumption habits were analysed statistically and by logistic regression. Results Univariate and multivariate logistic regression analysis of the relationship between age at menarche and gynaecological cancer (uterus/cervix/ovary cancer, the following gynecologic cancers in the article refer to having at least one of these three cancers) prevalence showed a negative association between age at menarche and malignancies of the uterus and ovaries prevalence (OR: 0.82, 95% CI 0.69–0.97), with a statistically significant difference ( p  = 0.02). Regression results of the association between age at menarche and different types of malignancies of the uterus and ovaries found a negative association between age at menarche and prevalence in uterine cancers ( P  = 0.03) and no association between age at menarche and prevalence in cervical and ovarian cancers ( P  = 0.17, P  = 0.29). Those with a younger age at menarche were more likely to develop uterine cancer (OR: 0.72, 95% CI 0.54–0.98). Conclusions There was a correlation between age at menarche and malignancies of the uterus and ovaries, with those who had menarche at an earlier age being at a higher risk of uterine cancer.

Anticancer effects of Erzhimaoling decoction in high-grade serous ovarian cancer in vitro and in vivo

Abstract Background High-grade serous ovarian cancer (HGSOC) is a common gynecologic malignancy with a poor prognosis. The traditional Chinese medicine formula Erzhimaoling decoction (EZMLD) has anticancer potential. This study aims to elucidate the anticancer effects of EZMLD on HGSOC in vitro and in vivo. Materials and methods EZMLD-containing serum was prepared from Sprague–Dawley rats for treating SKOV3 ovarian cancer cells at varying concentrations for 24 h and 48 h to determine the IC50. Concentrations of 0%, 5%, and 10% for 24 h were chosen for subsequent in vitro experiments. The roles of METTL3 and METTL14 in SKOV3 cells were explored by overexpressing these genes and combining EZMLD with METTL3/14 knockdown. Investigations focused on cell viability and apoptosis, apoptosis-related protein expression, and KRT8 mRNA m6A modification. For in vivo studies, 36 BALB/c nude mice were divided into six groups involving EZMLD (6.75, 13.5, and 27 g/kg) and METTL3 or METTL14 knockdowns, with daily EZMLD gavage for two weeks. Results In vitro, EZMLD-containing serum had IC50 values of 8.29% at 24 h and 5.95% at 48 h in SKOV3 cells. EZMLD-containing serum decreased SKOV3 cell viability and increased apoptosis. EZMLD upregulated METTL3/14 and FAS-mediated apoptosis proteins, while downregulating Keratin 8 (KRT8). EZMLD increased KRT8 mRNA m6A methylation. METTL3/14 overexpression reduced SKOV3 cell viability and increased apoptosis, while METTL3/14 knockdown mitigated EZMLD's effects. In vivo, EZMLD suppressed SKOV3 xenografts growth, causing significant apoptosis and modulating protein expression. Conclusions EZMLD has therapeutic potential for ovarian cancer and may be considered for other cancer types. Future research may explore its broader effects beyond cell apoptosis.

Establishment of an ovarian cancer exhausted CD8+T cells-related genes model by integrated analysis of scRNA-seq and bulk RNA-seq

AbstractOvarian cancer (OC) was the fifth leading cause of cancer death and the deadliest gynecological cancer in women. This was largely attributed to its late diagnosis, high therapeutic resistance, and a dearth of effective treatments. Clinical and preclinical studies have revealed that tumor-infiltrating CD8+T cells often lost their effector function, the dysfunctional state of CD8+T cells was known as exhaustion. Our objective was to identify genes associated with exhausted CD8+T cells (CD8TEXGs) and their prognostic significance in OC. We downloaded the RNA-seq and clinical data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. CD8TEXGs were initially identified from single-cell RNA-seq (scRNA-seq) datasets, then univariate Cox regression, the least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression were utilized to calculate risk score and to develop the CD8TEXGs risk signature. Kaplan–Meier analysis, univariate Cox regression, multivariate Cox regression, time-dependent receiver operating characteristics (ROC), nomogram, and calibration were conducted to verify and evaluate the risk signature. Gene set enrichment analyses (GSEA) in the risk groups were used to figure out the closely correlated pathways with the risk group. The role of risk score has been further explored in the homologous recombination repair deficiency (HRD), BRAC1/2 gene mutations and tumor mutation burden (TMB). A risk signature with 4 CD8TEXGs in OC was finally built in the TCGA database and further validated in large GEO cohorts. The signature also demonstrated broad applicability across various types of cancer in the pan-cancer analysis. The high-risk score was significantly associated with a worse prognosis and the risk score was proven to be an independent prognostic biomarker. The 1-, 3-, and 5-years ROC values, nomogram, calibration, and comparison with the previously published models confirmed the excellent prediction power of this model. The low-risk group patients tended to exhibit a higher HRD score, BRCA1/2 gene mutation ratio and TMB. The low-risk group patients were more sensitive to Poly-ADP-ribose polymerase inhibitors (PARPi). Our findings of the prognostic value of CD8TEXGs in prognosis and drug response provided valuable insights into the molecular mechanisms and clinical management of OC.

Functional analysis and validation of oncodrive gene AP3S1 in ovarian cancer through filtering of mutation data from whole-exome sequencing

Abstract Background High-grade serous ovarian carcinoma (HGSOC) is the most aggressive and prevalent subtype of ovarian cancer and accounts for a significant portion of ovarian cancer-related deaths worldwide. Despite advancements in cancer treatment, the overall survival rate for HGSOC patients remains low, thus highlighting the urgent need for a deeper understanding of the molecular mechanisms driving tumorigenesis and for identifying potential therapeutic targets. Whole-exome sequencing (WES) has emerged as a powerful tool for identifying somatic mutations and alterations across the entire exome, thus providing valuable insights into the genetic drivers and molecular pathways underlying cancer development and progression. Methods Via the analysis of whole-exome sequencing results of tumor samples from 90 ovarian cancer patients, we compared the mutational landscape of ovarian cancer patients with that of TCGA patients to identify similarities and differences. The sequencing data were subjected to bioinformatics analysis to explore tumor driver genes and their functional roles. Furthermore, we conducted basic medical experiments to validate the results obtained from the bioinformatics analysis. Results Whole-exome sequencing revealed the mutational profile of HGSOC, including BRCA1, BRCA2 and TP53 mutations. AP3S1 emerged as the most weighted tumor driver gene. Further analysis of AP3S1 mutations and expression demonstrated their associations with patient survival and the tumor immune response. AP3S1 knockdown experiments in ovarian cancer cells demonstrated its regulatory role in tumor cell migration and invasion through the TGF-β/SMAD pathway. Conclusion This comprehensive analysis of somatic mutations in HGSOC provides insight into potential therapeutic targets and molecular pathways for targeted interventions. AP3S1 was identified as being a key player in tumor immunity and prognosis, thus providing new perspectives for personalized treatment strategies. The findings of this study contribute to the understanding of HGSOC pathogenesis and provide a foundation for improved outcomes in patients with this aggressive disease.

LncRNA MAFG-AS1 is involved in human cancer progression

AbstractLong noncoding RNAs (lncRNAs) refer to a type of non-protein-coding transcript of more than 200 nucleotides. LncRNAs play fundamental roles in disease development and progression, and lncRNAs are dysregulated in many pathophysiological processes. Thus, lncRNAs may have potential value in clinical applications. The lncRNA, MAF BZIP Transcription Factor G (MAFG)-AS1, is dysregulated in several cancer, including breast cancer, lung cancer, liver cancer, bladder cancer, colorectal cancer, gastric cancer, esophagus cancer, prostate cancer, pancreatic cancer, ovarian cancer, and glioma. Altered MAFG-AS1 levels are also associated with diverse clinical characteristics and patient outcomes. Mechanistically, MAFG-AS1 mediates a variety of cellular processes via the regulation of target gene expression. Therefore, the diagnostic, prognostic, and therapeutic aspects of MAFG-AS1 have been widely explored. In this review, we discuss the expression, major roles, and molecular mechanisms of MAFG-AS1, the relationship between MAFG-AS1 and clinical features of diseases, and the clinical applications of MAFG-AS1.

Systematic review of the molecular basis of hereditary breast and ovarian cancer syndrome in Brazil: the current scenario

Abstract Background A detailed understanding of the genetic basis of cancer is of great interest to public health monitoring programs. Although many studies have been conducted in Brazil, a global view on the molecular profile related to hereditary breast and ovarian cancer (HBOC) in this large and heterogeneous population is lacking. Methods A systematic review following the PRISMA guidelines was conducted in three electronic databases (PubMed, BIREME and SciELO). Brazilian studies covering molecular analysis of genes related to HBOC, published until December 2023, were considered. Results We identified 35 original studies that met all the inclusion criteria. A total of 137 distinct mutations were found in the BRCA1 gene, but four of them corresponded to 44.5% of all mutations found in this gene. The c.5266dupC BRCA1 mutation was responsible for 26.8% of all pathogenic mutations found in the BRCA1 gene in patients with clinical criteria for HBOC from the Brazilian population. Considering all studies that track this mutation in the BRCA1 gene, we found a frequency of 2% (120/6008) for this mutation in Brazilian patients. In the BRCA2 gene, the four most frequent mutations corresponded to 29.2% of pathogenic mutations. Even though it was tracked by few studies, the c.156_157insAlu mutation was responsible for 9.6% of all pathogenic mutations reported in the BRCA2 gene. Seventeen studies found pathogenic mutations in other non-BRCA genes, the c.1010G &gt; A mutation in the TP53 gene being the most frequent one. Considering all studies that screened for this specific mutation in patients with the clinical criteria for HBOC, the frequency of c.1010G &gt; A was estimated at 1.83% (61/3336). Conclusions Despite significant molecular heterogeneity among mutations in HBOC patients from Brazil, three mutations deserve to be highlighted, c.5266dupC, c.156_157insAlu and c.1010G &gt; A in the BRCA1, BRCA2 and TP53 genes, respectively. With more than 200 records, these three mutations play a vital role in the pathology of breast and ovarian cancer in Brazil. The data collected shed light on the subject, but there is still not enough data from certain subpopulations.

Predictive value of the Adult Comorbidity Evaluation 27 on adverse surgical outcomes and survival in elderly with advanced epithelial ovarian cancer undergoing cytoreductive surgery

Abstract Objective We aimed to evaluate the ability of Adult Comorbidity Evaluation 27 (ACE-27) to predict perioperative outcomes and survival in elderly women with advanced epithelial ovarian cancer (AEOC) undergoing cytoreductive surgery. Methods We collected patients with AEOC in our hospital between January 1, 2012 and January 1, 2021. Patients younger than 65 years old or those with non-epithelial ovarian cancer were excluded. ACE-27 was applied retrospectively to assess comorbidities in the selected patients, who were then classified into two groups based on their ACE-27 scores: low ACE-27 score group (none to mild) and high ACE-27 score group (moderate to severe). Results A total of 222 elderly women with AEOC were included, of whom 164 patients accepted debulking surgery. Among those who have undergone surgery, Clavien–Dindo grade III + perioperative complications or unintended intensive care unit (ICU) admission occurred more often in patients of high ACE-27 score group, with statistically significant difference (odds ratio [OR]: 4.21, 95% confidence interval [CI], 1.28–14.35, p  = 0.018). Further stratified analyses by age, BMI, FIGO stage and pathology also prove that OS of patients graded severe was shorter than patients graded none to moderate in cohort of age &lt; 70, BMI &lt; 25 kg/m 2 , FIGO III stage and pathology of serous, respectively. Kaplan–Meier survival curves analyzed by log-rank test showed that the overall survival (OS) of patients with severe comorbidities were shorter than with none to moderate (HR 3.25, 95%CI 1.55–6.79, p = 0.002). Conclusions Our findings demonstrate the ability of ACE-27 to predict grade III + perioperative complications or unintended ICU admission and survival in elderly patients with AEOC. This highlights the possibility for ACE-27 to play an instrumental role in identifying AEOC patients who are more susceptible to adverse surgical outcomes and have a poor survival rate and assisting in decisions regarding treatment.

Identification of the prognostic value of LACTB2 and its correlation with immune infiltrates in ovarian cancer by integrated bioinformatics analyses

AbstractOvarian cancer (OC) is one of the most common reproductive tumors in women, whereas current treatment options are limited. β-lactamase-like-protein 2 (LACTB2) has been observed to be associated with various cancers, but its function in OC is unknown. Therefore, we evaluate the prognostic value and the underlying function of LACTB2 in OC. In this study, high expression of LACTB2 was observed in OC compared with normal controls. Kaplan–Meier Plotter analysis revealed that overexpressed LACTB2 is strongly correlated with poor prognosis. We conducted GO/KEGG analysis to investigate the potential biological function of LACTB2 in OC. GESA analysis showed that LACTB2 was closely related to immune-related pathways. Subsequently, we explored the relationship between LACTB2 and 24 types of immune cells in OC. The results suggested that LACTB2 was positively associated with multiple tumor-infiltrating immune cells. Importantly, LACTB2 may modulate immune cell infiltration in OC to influence prognosis. In conclusion, LACTB2 can be used as a promising prognostic biomarker and immunotherapy target for OC.

Exploring the role of circular RNAs in endometrial cancer progression and chemoresistance: Implications for targeted therapies

Abstract Endometrial cancer stands as a prevalent malignant tumor of the female genital tract, while showing growing incidence statistics. Circular RNAs (circRNAs) demonstrate translational value as biomarkers and therapeutic targets in endometrial cancer because they affect chemoresistance and tumor progression through miRNA interactions, which makes them attractive candidates for non-invasive diagnostic tools and targeted medical approaches. Through their miRNA sponge activity, they regulate gene expression together with their ability to modulate RNA-binding proteins, affect mRNA stability and impact the PTEN/PI3K/Akt and MAPK pathways that enable tumor growth and survival. The study demonstrates how circRNAs function through multiple mechanisms in endometrial cancer development, yet indicates their value as therapeutic targets for disease management. The paper explores how recent developments utilize circRNA strategies to combat chemoresistance alongside improving targeted therapy research. Future research must focus on optimizing detection methods while developing standardized diagnostic procedures and performing large-scale validation studies to establish clinical utility.

Development and validation of an individualized gene expression-based signature to predict overall survival of patients with high-grade serous ovarian carcinoma

Abstract Background High-grade serious ovarian carcinoma (HGSOC) is a subtype of ovarian cancer with a different prognosis attributable to genetic heterogeneity. The prognosis of patients with advanced HGSOC requires prediction by genetic markers. This study systematically analyzed gene expression profile data to establish a genetic marker for predicting HGSOC prognosis. Methods The RNA-seq data set and information on clinical follow-up of HGSOC were retrieved from Gene Expression Omnibus (GEO) database, and the data were standardized by DESeq2 as a training set. On the other hand, HGSOC RNA sequence data and information on clinical follow-up were retrieved from The Cancer Genome Atlas (TCGA) as a test set. Additionally, ovarian cancer microarray data set was obtained from GEO as the external validation set. Prognostic genes were screened from the training set, and characteristic selection was performed using the least absolute shrinkage and selection operator (LASSO) with 80% re-sampling for 5000 times. Genes with a frequency of more than 2000 were selected as robust biomarkers. Finally, a gene-related prognostic model was validated in both the test and GEO validation sets. Results A total of 148 genes were found to be significantly correlated with HGSOC prognosis. The expression profile of these genes could stratify HGSOC prognosis and they were enriched to multiple tumor-related regulatory pathways such as tyrosine metabolism and AMPK signaling pathway. AKR1B10 and ANGPT4 were obtained after 5000-time re-sampling by LASSO regression. AKR1B10 was associated with the metastasis and progression of several tumors. In this study, Cox regression analysis was performed to create a 2-gene signature as an independent prognostic factor for HGSOC, which has the ability to stratify risk samples in all three data sets (p &lt; 0.05). The Gene Set Enrichment Analysis (GSEA) discovered abnormally active REGULATION_OF_AUTOPHAGY and OLFACTORY_TRANSDUCTION pathways in the high-risk group samples. Conclusion This study resulted in the creation of a 2-gene molecular prognostic classifier that distinguished clinical features and was a promising novel prognostic tool for assessing the prognosis of HGSOC. RiskScore was a novel prognostic model which might be effective in guiding accurate prognosis of HGSOC.

Diagnostic value of a CT-based radiomics nomogram for discrimination of benign and early stage malignant ovarian tumors

Abstract Background This study aimed to identify the diagnostic value of models constructed using computed tomography-based radiomics features for discrimination of benign and early stage malignant ovarian tumors. Methods The imaging and clinicopathological data of 197 cases of benign and early stage malignant ovarian tumors (FIGO stage I/II), were retrospectively analyzed. The patients were randomly assigned into training data set and validation data set. Radiomics features were extracted from images of plain computed tomography scan and contrast-enhanced computed tomography scan, were then screened in the training data set, and a radiomics model was constructed. Multivariate logistic regression analysis was used to construct a radiomic nomogram, containing the traditional diagnostic model and the radiomics model. Moreover, the decision curve analysis was used to assess the clinical application value of the radiomics nomogram. Results Six textural features with the greatest diagnostic efficiency were finally screened. The value of the area under the receiver operating characteristic curve showed that the radiomics nomogram was superior to the traditional diagnostic model and the radiomics model (P &lt; 0.05) in the training data set. In the validation data set, the radiomics nomogram was superior to the traditional diagnostic model (P &lt; 0.05), but there was no statistically significant difference compared to the radiomics model (P &gt; 0.05). The calibration curve and the Hosmer–Lemeshow test revealed that the three models all had a great degree of fit (All P &gt; 0.05). The results of decision curve analysis indicated that utilization of the radiomics nomogram to distinguish benign and early stage malignant ovarian tumors had a greater clinical application value when the risk threshold was 0.4–1.0. Conclusions The computed tomography-based radiomics nomogram could be a non-invasive and reliable imaging method to discriminate benign and early stage malignant ovarian tumors.

Application of nanoparticles in the therapeutic management of endometrial cancer

The management of endometrial cancer (EC) remains challenging due to metastatic risk, therapeutic resistance, and the modest durability of standard regimens. Nanotechnology offers a promising avenue to overcome these limitations by enhancing tumor-selective drug delivery, enabling controlled release, and facilitating multimodal approaches that integrate therapy and imaging. This review systematically summarizes recent advances in nanoparticle applications for EC, focusing on strategies that target key molecular drivers, such as TP53, PI3K/PTEN, and immune checkpoints, and evaluates localized administration routes such as vaginal delivery. Preclinical studies, including the demonstration of JX06-loaded nanoparticles combined with metformin achieving approximately 86% viability inhibition in patient-derived EC cells, underscore the potential of nanoformulations to improve intracellular delivery and therapeutic efficacy. However, current research remains constrained by its reliance on limited cell lines and immunodeficient animal models. Clinically validated active targeting efficacy has yet to be established in EC, and translational progress is further hindered by the inconsistent enhanced permeability and retention (EPR) effect, accelerated blood clearance upon repeated dosing, as well as manufacturing and regulatory challenges. Through rational design of the targeting functionality and controlled-release properties of nanocarriers, combined with EC-specific disease models and biomarker-guided clinical trials, nanotechnology holds promise for overcoming existing therapeutic limitations. With continued advancement in translational research, nanotherapeutic platforms are expected to synergize with surgery, radiotherapy, and systemic treatments, thereby paving the way for more durable and personalized therapeutic options for EC patients. This review systematically summarizes the latest research progress in nanotechnology for EC treatment, providing a solid theoretical foundation and clear research directions to accelerate the clinical translation of nanomedicine in this field.

Quercetin inhibits the progression of endometrial HEC-1-A cells by regulating ferroptosis—a preliminary study

Abstract Background Endometrial carcinoma (EC) is one of the most common female reproductive system tumors, which seriously threatens women's health. This preliminary study aimed to investigate the effects of quercetin on the EC cells and explore the potential mechanism. Methods In this study, the effects of quercetin on endometrial cancer HEC-1-A cells were studied by a series of cell biological methods, including CCK-8 detection of cell activity, Western blotting of ferroptosis-related proteins, apoptosis detection, reactive oxygen species (ROS) detection and other detections. Results Our results showed that quercetin inhibited the proliferation and migration of EC cells, induced cell apoptosis, and affected the cell cycle. Furthermore, the anti-tumor effect of quercetin was related to the induction of ferroptosis in the EC cells. Conclusions Our study shows quercetin may exert anti-tumor effects, which may be related to the regulation of ferroptosis. Our study provides evidence for the future treatment of EC with small molecule drugs.

The impact of lymphovascular space invasion on survival in early stage low-grade endometrioid endometrial cancer

Abstract Background The lymphovascular space invasion (LVSI) is suggested as a prognostic factor for endometrial cancer in many studies, but it has not yet been employed in FIGO staging system. The present study was aimed to evaluate the impact of LVSI on survival in patients with early stage endometrioid endometrial cancer. Methods This retrospective cohort was conducted on early stage endometrial cancer patients who underwent surgical staging [total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH/BSO)] and omental biopsy at Referral Teaching Hospitals of Tehran from 2005 to 2021. Patient’s age, menopause status, tumor grade, tumor size, depth of myometrial invasion, LVSI and lower segment involvement were recorded. Data were analyzed with SPSS 22. Results 415 patients with stage I and grade 1–2, endometrioid endometrial cancer were analyzed. 100 patients (24.1%) were LVSI-positive. 3-year and 5-year survival rates were 97.1% and 88.9%, respectively. Recurrence occurred in 53 patients (12.8%). 3-year overall survival rates in LVSI-negative and LVSI-positive were 98.7% and 92%. These rates for 5-year survival were 92.1% and 79%, respectively. Recurrence rates in LVSI-negative were 8.9% while it was 25% in LVSI-positive cases. Multivariate analysis showed that LVSI has significant correlation with 3-year and 5-year overall survival rates. Conclusions LVSI in early stage endometrial cancer significantly and independently influences 3-year and 5-year survival rates and acts as a strong prognostic factor in these patients. LVSI should be implemented in endometrial cancer staging systems due to its significant correlation with cancer recurrence rates and 5-year survival rates.

Circular RNA hsa_circ_0023404 promotes the proliferation, migration and invasion in endometrial cancer cells through regulating miR-217/MAPK1 axis

Abstract Background Emerging studies indicated that circular RNA hsa_circ_ 0023404 and its target miR-217/MARK1 axis play a critical role in cancer progression such as non-small cell lung cancer and cervical cancer. However, the role of hsa_circ_0023404/miR-217/MARK1 involved in endometrial cancer (EC) was not investigated yet. The aim of this study is to investigate the functions of hsa_circ_0023404 in endometrial cancer (EC) and the potential molecular mechanism. Methods We used RT-qPCR and Western blot approach to detect the expressed levels of related genes in EC cell lines. Transfected siRNAs were applied to knockdown the level of related mRNA in cells. Cell proliferation by CCK-8 assay and colony formation assay were applied to detect cell proliferation. Transwell migration and invasion assay was for detecting the migration and invasion of the cells. Results RT-qPCR showed that the levels of hsa_circ_0023404 and MARK1 mRNA were upregulated, but mirR-217 was decreased in three endometrial cancer cell lines. Knockdown of hsa_circ_0023404 by siRNA markedly increased the level of miR-217 and reduced the proliferation of the Ishikawa cells. It also inhibited the cell migration and invasion. Anti-miR-217 can reverse the promoted proliferation, migrations and invasion of Ishikawa cells mediated by si-circ_0023404. si-MARK1 restored the inhibited cell proliferation, migration and invasion of the co-transfected Ishikawa cells with si- circ_0023404 and anti-miR-217. Conclusion hsa_circ_0023404 exerts a tumor-promoting role in endometrial cancer by regulating miR-217/MARK1 axis. hsa_circ_0023404 inhibit miR-217 as sponge which inhibit endometrial cancer cell growth and metastasis. MARK1 is downstream target of miR217 and upregulated by hsa_circ_ 0023404/miR-217 axis and involved in the endometrial cancer progression.

CircWDR26 regulates endometrial carcinoma progression via miR-212-3p-mediated typing genes MSH2

Abstract Background Circular RNAs (circRNA) are important in mediating tumor progression, but their roles in endometrial carcinoma (EC) are not fully understood yet. Many circRNAs are dysregulated and may contribute to EC progression. The functions of circWDR26 in EC remain unknown. Methods The expression of circWDR26 in EC and adjacent normal tissues, and cell lines was determined by qPCR. The proliferation, apoptosis, migration, and invasion of EC cells was examined by CCK-8 assay, flow cytometry, wound healing assay and Transwell assay. The interaction between circWDR26, MSH2 and miR-212-3p was determined by luciferase assay. EC cells were inoculated into nude mice and tumor burden was determined by measuring tumor dimensions, size, and weight. The proliferative marker Ki67 in EC tissue was determined by immunohistochemistry. Results The expression of circWDR26 in EC tissues or cell lines was higher than in the normal tissue or endometrial epithelial cells. Downregulation of circWDR26 resulted in attenuated proliferation, increased apoptosis, reduced migration and invasion of EC cells. Mechanistically, circWDR26 targeted and suppressed the expression of miR-212-3p. We further found that MSH2 was the novel target of miR-212-3p and was upregulated by circWDR26 via inhibiting miR-212-3p. In vivo experiment demonstrated that circWDR26 was essential for EC tumor growth. Conclusion circWDR26 promoted EC progression by regulating miR-212-3p/MSH2 axis and provided novel insights into anti-cancer treatment.

A study on strategies to optimize bladder volume consistency in radiotherapy patients

This study aimed to investigate the impact of multi-step workflow optimization on enhancing the consistency of bladder volume among patients receiving pelvic radiotherapy. Patients requiring bladder preparation were selected through simple random sampling before and after the implementation of optimization measures in June 2024. Each cohort included 5 patients with prostate cancer, 15 with cervical cancer, and 10 with rectal cancer cases. Statistical methods were used to evaluate the correlation and consistency between bladder volume measured by cone-beam CT (V Pearson correlation analysis showed that a strong correlation between V Multi-step workflow optimization reduced the standard deviation of differences between CBCT-derived and scanner-derived bladder volumes (V

Correlation and combined predictive value analysis of serum IL-6 and IL-10 levels with tumor progression in patients with cervical cancer

To investigate correlation between interleukin-6 (IL-6) and interleukin-10 (IL-10) levels in the serum of patients with cervical cancer and tumor progression, and to quantify predictive value of combined detection of two for prognosis. A total of 80 cervical cancer patients treated in our hospital from June 2020 to December 2022 were retrospectively selected as the cervical cancer group. Following the principle of 1:1:1, 80 healthy subjects were selected as controls, and 80 benign patients detected by pathological examination were selected as the benign group. The changes in serum levels of IL-6 and IL-10 among the three groups were compared. Patients were followed up and further divided into a progressive group of 38 cases and a non-progressive group of 42 cases based on whether they experienced disease progression. Clinical data of included subjects were analyzed, such as patient age, pathological type, differentiation degree, TNM staging, etc. The influencing factors of disease progression were assessed using a COX regression model. ROC curves were applied to analyze predictive value of serum IL-6 and IL-10 detection alone or in combination for disease progression. These subjects were followed up for 24 months, and relationship between IL-6, IL-10, and survival was assessed using Kaplan Meier survival curve. Patients in the benign group had much higher IL-6 and IL-10 serum levels than those in the control group (P  71.47 ng/mL), IL-10 low expression group (≤ 14.30 pg/mL), and IL-10 high expression group (> 14.30 pg/mL). Kaplan Meier survival curve analysis proved that median survival time of IL-6 and IL-10 low expression was higher than that of IL-6 and IL-10 high expression (IL-6 28.5 vs .12.5, IL-10 25.5 vs. 15.0) (P = 0.018). Serum IL-6 and IL-10 levels in patients with cervical cancer were raised. COX multivariate analysis stated that there was an independent association between the two and the disease progression, and they might be potential biomarkers for evaluating the disease progression. The levels of the two were positively correlated. The AUC of the combined detection was 0.883, suggesting that it owned certain predictive value for disease progression, and its clinical application needed further verification.

The intersection of ferroptosis and non-coding RNAs: a novel approach to ovarian cancer

Understanding the core principles of ovarian cancer has been significantly improved through the exploration of Ferroptosis, a type of cell death triggered by iron that leads to an increase in lipid peroxides. Current research has shed light on the critical functions of non-coding RNAs, such as circRNAs, lncRNAs, and miRNAs, in regulating ferroptosis in ovarian cancer. The aim of this paper is to comprehensively analyze how ncRNAs influence the development of ferroptosis in ovarian cancer cells. In-depth exploration is undertaken to understand the intricate ways in which ncRNAs regulate essential elements of ferroptosis, including iron management and lipid peroxidation levels. We also investigate their significant involvement in the progression of this type of cellular demise. It should be emphasized that ncRNAs can impact the synthesis of crucial proteins, such as GPX4, a key contributor to the cellular defense against oxidation, and ACSL4, involved in lipid formation. In addition, we examine the correlation between ncRNAs and well-known pathways associated with oxidative stress and cell death. The consequences of these discoveries are noteworthy, since focusing on particular ncRNAs could potentially render ovarian cancer cells more vulnerable to ferroptosis, effectively combating drug resistance problems. This discussion highlights the growing significance of ncRNAs in governing ferroptosis and their potential as useful biomarkers and treatment targets for ovarian cancer. We intend to promote additional research into the involvement of ncRNAs in controlling ferroptosis, based on current findings, with the ultimate goal of informing targeted therapeutic strategies and improving long-term treatment outcomes for individuals suffering from OC.

Squamous cell carcinoma antigen levels in women with cervical cancer and those without cervical cancer: a cross-sectional study among women of African descent

Globally, cervical cancer is one of the most common cancers among females with 604,000 new cases and 342,000 deaths annually. It is a disease of public health importance. Detection of a tumour-specific antigen may be useful in the detection and early management of the disease. The squamous cell carcinoma antigen, a glycoprotein produced in squamous epithelial cells, could serve as a tumour marker in the diagnosis and management of cervical cancer. The aim of this study was to compare the serum levels of squamous cell carcinoma antigen in women with cervical cancer with normal non-cancerous controls and to identify its clinical and sociodemographic correlates. This was a comparative cross-sectional study between women with histologically confirmed squamous cell carcinoma of the cervix and women without cervical cancer at the University of Benin Teaching Hospital in Nigeria. Eighty women were recruited for the study, which consisted of 40 cases of cervical cancer and a comparative group of 40 women without cervical cancer. Levels of squamous cell carcinoma antigen were determined by enzyme-linked immunosorbent assay (ELISA). Data were analysed using the Statistical Package for Social Sciences (SPSS) for Windows, version 27. There was a statistically significant difference in the mean squamous cell carcinoma antigen levels in women with cervical cancer (0.7 ± 0.5 ng/ml) and those without cervical cancer (0.4 ± 0.2 ng/ml) (p = 0.0003). Using a cut-off value of 0.45, the sensitivity of SCCA was 75% while specificity was 70%. Its positive predictive value was71.4% while the negative predictive value was 73.7%. The stage of disease, parametrial involvement, metastasis, body mass index, age, parity, alcohol consumption and menopausal status did not significantly affect levels of the tumour marker. The serum levels of squamous cell carcinoma antigen are elevated in Nigerian women with cervical cancer compared to those without cervical cancer. Sociodemographic factors and extent of disease do not appear to significantly affect levels of the tumour marker.

The diagnostic value of transvaginal sonoelastography for cervical cancer and cervical intraepithelial neoplasia: a systematic review and meta-analysis

To assess the accuracy of transvaginal sonoelastography (TVSE) for diagnosis of cervical cancer (CC) and cervical intraepithelial neoplasia (CIN). A search was done inPubmed, Embase, Web of Science, Cochrane Library, Wanfang, VIP, China National Knowledge Infrastructure (CNKI), and SinoMed from inception to May 9, 2025. TVSE was compared with histopathology regarding diagnostic accuracy. The diagnostic accuracy of TVSE was assessed by calculated pooled sensitivity (SEN)/specificity (SPE), diagnostic odds ratio (DOR), and area under the curve. Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) was used for quality assessment. The relevant data were statistically analyzed using Meta-Disc 1.4 and Stata 15.0. Eighteen references (studies) were included. They involved a total of 1738 patients, including 863 ones with CC and 875 ones with CIN. TVSE had a pooled SEN of 0.90 [95% confidence interval (CI) 0.87-0.92], a pooled SPE of 0.88 (95% CI 0.85-0.92), and an area under the summary receiver operating characteristic (SROC) curve (AUC) of 0.94 (95% CI 0.91-0.95). The results of subgroup analysis showed imaging modalities as a source of heterogeneity, with an AUC of 0.91 (95% CI 0.88-0.93) for shear wave elastography (SWE), and an AUC of 0.93 (95% CI 0.90-0.95) for strain elastography (SE). TVSE is of relatively high value for differential diagnosis of CC and CIN. The diagnostic accuracy of SE and SWE is similar. Given the limitations of this study and to further explore the sources of heterogeneity, more multicenter high-quality studies including large numbers of participants are required to further confirm the effectiveness of TVSE.

Cross-talk between cuproptosis and ferroptosis to identify immune landscape in cervical cancer for mRNA vaccines development

Messenger RNA (mRNA)-based vaccines present a promising avenue for cancer immunotherapy; however, their application in cervical cancer remains unexplored. This study investigated the interplay between the regulated cell death pathways of cuproptosis and ferroptosis to advance the development of mRNA vaccines for cervical cancer. We identified key cuproptosis-related and ferroptosis-related genes (CFRGs) from public mRNA profiles and determined their prognostic significance, mutation frequencies, and effect on the immune landscape. Our analysis revealed two distinct subtypes of cervical cancer associated with CFRGs, with differences in prognosis and immune characteristics. Using LASSO, XGBoost, and SVM-RFE methods, we established a 4-gene prognostic signature (TSC22D3, SQLE, ZNF419, and TFRC) to stratify patients based on their risk and determine its correlation with immune microenvironment, mutation profiles, and treatment responses. RT-qPCR validation confirmed the differential expression of these genes in clinical samples. Our findings identify TSC22D3, SQLE, ZNF419, and TFRC as candidate targets for mRNA vaccine development and offer a potential prognostic tool for personalized cervical cancer treatment.

M2-type tumor-associated macrophages upregulated PD-L1 expression in cervical cancer via the PI3K/AKT pathway

Abstract Background and purpose PD-1/PD-L1 inhibitors have become a promising therapy. However, the response rate is lower than 30% in patients with cervical cancer (CC), which is related to immunosuppressive components in tumor microenvironment (TME). Tumor-associated macrophages (TAMs), as one of the most important immune cells, are involved in the formation of tumor suppressive microenvironment. Therefore, it will provide a theoretical basis for curative effect improvement about the regulatory mechanism of TAMs on PD-L1 expression. Methods The clinical data and pathological tissues of CC patients were collected, and the expressions of PD-L1, CD68 and CD163 were detected by immunohistochemistry. Bioinformatics was used to analyze the macrophage subtypes involved in PD-L1 regulation. A co-culture model was established to observe the effects of TAMs on the morphology, migration and invasion function of CC cells, and the regulatory mechanism of TAMs on PD-L1. Results PD-L1 expression on tumor cells could predict the poor prognosis of patients. And there was a strong correlation between PD-L1 expression with CD163+TAMs infiltration. Similarly, PD-L1 expression was associated with M1/M2-type TAMs infiltration in bioinformatics analysis. The results of cell co-culture showed that M1/M2-type TAMs could upregulate PD-L1 expression, especially M2-type TAMs may elevate the PD-L1 expression via PI3K/AKT pathway. Meanwhile, M1/M2-type TAMs can affect the morphological changes, and enhance migration and invasion abilities of CC cells. Conclusions PD-L1 expression in tumor cells can be used as a prognostic factor and is closely related to CD163+TAMs infiltration. In addition, M2-type TAMs can upregulate PD-L1 expression in CC cells through PI3K/AKT pathway, enhance the migration and invasion capabilities, and affect the tumor progression.

Predictors of cervical tumour size for outpatients with cervical cancer at the University of Gondar referral hospital: a retrospective study design

Abstract Background Cervical cancer is one of the most serious threats to women's lives. Modelling the change in tumour size over time for outpatients with cervical cancer was the study's main goal. Methods A hospital conducted a retrospective cohort study with outpatients who had cervical cancer. The information about the tumour size was taken from the patient's chart and all patient data records between May 20, 2017, and May 20, 2021. The data cover 322 cervical cancer outpatients' basic demographic and medical information. When analysing longitudinal data, the linear mixed effect model and the connection between tumour sizes in outpatients were taken into consideration. A linear mixed model, a random intercept model, and a slope model were used to fit the data. Result A sample of 322 cervical cancer outpatients was examined, and 148 (or 46% of the outpatients) tested positive for HIV. The linear mixed model with a first-order autoregressive covariance structure revealed that a change in time of one month led to a 0.009 cm2 reduction in tumour size. For every kilogramme more in weight, the tumour size change in cervical cancer patients decreased considerably by 0.0098 cm2. The tumour size change in the cervical cancer patient who was HIV-positive was 0.4360 cm squared greater than that in the HIV-negative outpatients. Conclusion As a consequence, there was a significant association between the longitudinal change in tumour size and the predictor variables visit time, therapy, patient weight, cancer stage, HIV, oral contraceptive use, history of abortion, and smoking status.

Research progress on the GRP78 gene in the diagnosis, treatment and immunity of cervical cancer

AbstractBackgroundGRP78 is a molecular chaperone protein in the endoplasmic reticulum that is involved in protein assembly and quality control, and it participates in ER stress regulation of endoplasmic reticulum stress pathways. Studies have confirmed that GRP78 gene is highly expressed in a variety of tumors and is involved in different biological functions.PurposeThe present review highlights the involvement of the GRP78 gene in regulating the development of cervical cancer by promoting the proliferation and invasion of cervical cancer cells as well as by inhibiting apoptosis and promoting the Warburg effect. High expression of GRP78 is positively correlated with chemotherapy resistance in cervical cancer. GRP78 plays an anticancer role in cervical cancer by regulating autophagy and apoptosis. Mediated immune CD8 + T cells regulate tumor cell immunity and play a role in the application of the HPV vaccine.ConclusionsGRP78 plays a multifunctional role in cervical cancer and has important therapeutic and diagnostic value.

Exosomal NOX1 promotes tumor-associated macrophage M2 polarization-mediated cancer progression by stimulating ROS production in cervical cancer: a preliminary study

Abstract Background Cervical cancer the fourth most frequently diagnosed cancer and the fourth leading cause of cancer death in women, with an estimated 604,000 new cases and 342,000 deaths worldwide in 2020 for high rates of recurrence and metastasis. Identification of novel targets could aid in the prediction and treatment of cervical cancer. NADPH oxidase 1 (NOX1) gene-mediated production of reactive oxygen species (ROS) could induce migration and invasion of cervical cancer cells. Tumor-associated macrophages (TAMs) play important roles in cervical cancer. Tumor cell-derived exosomes mediate signal transduction between the tumor and tumor microenvironment. Elucidation of the mechanisms of NOX1-carrying exosomes involved in the regulation of TAMs may provide valuable insights into the progression of cervical cancer. Methods Uniformly standardized mRNA data of pan-carcinoma from the UCSC database were downloaded. Expression of NOX1 in tumor and adjacent normal tissues for each tumor type was calculated using R language software and significant differences were analyzed. SNP data set were downloaded for all TCGA samples processed using MuTect2 software from GDC. Cell experiment and animal tumor formation experiment were used to evaluate whether exosomal NOX1 stimulating ROS production to promote M2 polarization of TAM in cervical cancer. Results NOX1 is highly expressed with a low mutational frequency in pan-carcinoma. Upregulation of NOX1 may be associated with infiltration of M2-type macrophages in cervical cancer tissues, and NOX1 promotes malignant features of cervical cancer cells by stimulating ROS production. Exosomal NOX1 promotes M2 polarization of by stimulating ROS production. Exosomal NOX1 enhances progression of cervical cancer and M2 polarization in vivo by stimulating ROS production. Conclusion Exosomal NOX1 promotes TAM M2 polarization-mediated cancer progression through stimulating ROS production in cervical cancer.

ROS-mediated cell death and phase separation in gynecological malignancies

Abstract Reactive oxygen species (ROS) are reactive products of cellular metabolism that, under physiological conditions, activate specific signaling pathways essential for cellular functions. Excessive accumulation of ROS overwhelms cellular antioxidant defenses, leading to functional damage or cell death. ROS-mediated cell death manifests in multiple forms, including apoptosis, ferroptosis, immunogenic cell death, pyroptosis, oxeiptosis, NETosis, and parthanatos. In gynecological malignancies, inducing ROS-mediated cell death is proposed as a therapeutic strategy. Furthermore, research indicates that excessive ROS promotes abnormal phase separation, resulting in functional damage to tumor cells. Therefore, ROS-mediated cell death and phase separation provide a new entry point for preventing tumorigenesis or treating gynecological malignancies. In this review, we summarize the mechanisms underlying ROS-mediated cell death and phase separation, and describe innovative strategies based on ROS that hold promise for treating gynecological malignancies. This review will also discuss controversial issues in tumor therapeutics, including the paradoxical roles of ROS manipulation. This will offer new insights into the management of gynecological malignancies, providing theoretical support for clinical practice.

Fertility-sparing treatment for low-grade endometrial stromal sarcoma

A multicenter deep learning framework integrating radiomics and vision transformers for comprehensive ovarian tumor analysis from ultrasound imaging

NETs in ovarian cancer progression: innovative nanoparticle-based therapeutic strategies

Ovarian cancer is an aggressive and heterogeneous malignancy characterized by genetic diversity, clonal evolution, and rapid development of therapeutic resistance, representing a major global clinical challenge. Neutrophils actively drive disease progression by fostering tumor growth, angiogenesis, immune evasion, and metastasis through the formation of neutrophil extracellular traps (NETs). NETs accelerate epithelial-to-mesenchymal transition (EMT), remodel the extracellular matrix (ECM), and prime pre-metastatic niches, creating a permissive environment for metastatic dissemination. Elevated NET levels correlate with advanced disease and poor prognosis, positioning them as powerful diagnostic and prognostic biomarkers. To exploit this vulnerability, we propose a multifunctional nanoparticle platform co-delivering GSK484, a selective anti-NETosis agent, alongside a potent cytotoxic drug. Engineered for tumor-selective targeting and pH-responsive release, this system dismantles the NET-rich tumor microenvironment while directly eradicating cancer cells, maximizing local efficacy and minimizing systemic toxicity. By simultaneously neutralizing the NET-modified niche and attacking tumor cells, this strategy has the potential to overcome chemoresistance, block metastatic spread, and enable precision-guided therapy. Implementation of this approach could refine patient stratification, enhance response rates, reduce recurrence, and translate into tangible survival benefits. This review highlights NETs as central orchestrators of ovarian cancer progression and presents a translationally actionable nanomedicine strategy poised to transform clinical outcomes in a malignancy long plagued by therapeutic failure.

EMSY enhances glycolysis in ovarian cancer cells

Abstract EMSY is critical in the progression of ovarian cancer; nevertheless, its impact on tumor metabolism is not widely known. This study showed ovarian cancer cells overexpressing EMSY produce more lactate and have upregulated LDHA expression; the promoting effect of EMSY on the malignant phenotype of these cells is eliminated when LDHA expression is knocked down or glycolysis is inhibited in ovarian cancer cells. Mechanistic studies revealed that EMSY interacts with β-catenin, and the knockdown of EMSY inhibits the transcriptional activation of LDHA by β-catenin. In summary, this study identifies EMSY’s metabolic regulatory role in ovarian cancer cells and offers treatment of ovarian cancer with a new therapeutic target.

Tumor markers level profile in dermatomyositis, systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis and ovarian cancer

Abstract Background Autoimmune diseases (AID) have been showed to be susceptibility to malignancy. This study aimed to analyzed the profile of serum tumor markers in four common autoimmune disease. Methods Patients with dermatomyositis (DM, n = 132), Systemic sclerosis (SSc, n = 77), Systemic lupus erythematosus (SLE, n = 191), Rheumatoid arthritis (RA, n = 160) and ovarian cancer (n = 250) were included in this study. Twelve tumor markers (CA724, AFP, FRT, NSE, CA19-9, CA125, CYFRA21-1, CA153, β-HCG and HE4) levels and abnormal rate in these patients were retrospective statistics. The tumor markers profiles were compared among the different AID. Results Compared with ovarian cancer (OV) patients, there were no significant differences for the levels and abnormal rates of CYFRA21-1/HE4/CA50/FRT in AID patients. The levels and abnormal rates of CA724/FRT/CA125/NSE were higher in OV patients than that in AID patients. 75% AID patients have at least one elevated tumor marker. 69.46% AID patients have 2–5 elevated tumor markers. All the 12 tumor markers were negative in 16.67, 19.74, 27.23 and 32.70% of DM, SSc, SLE and RA patients. Except CA50, the levels of the other eleven tumor markers were significantly different between DM/SSc/SLE/RA. Except AFP/β-HCG/SCC, the abnormal rate of the other tumor markers were significantly different between these AID. Conclusions The increased levels of tumor makers were common in four major AID, and the profile of tumor makers were significantly different among these AID.

Identification of HOXB9 to predict prognosis of endometrial cancer based on comprehensive bioinformatics analysis

Abstract Background The HOXB9 gene, which plays a key role in embryonic development, is also involved in the regulation of various human cancers. However, the potential relationship between HOXB9 and endometrial cancer (EC) has not yet been comprehensively analyzed and fully understood. Methods We used multiple bioinformatics tools to explore the role of HOXB9 in EC. Results The expression of HOXB9 was significantly upregulated in pan-cancer, including EC (P &lt; 0.05). Quantitative real time polymerase chain reaction (qRT-PCR) experiment confirmed the high expression of HOXB9 in EC from clinical samples (P &lt; 0.001). Double validated by Enrichr and Metascape, HOXB9 showed a strong correlation with HOX family, suggesting that HOX family may also involve in the development of EC (P &lt; 0.05). Enrichment analysis revealed HOXB9 is mainly associated with cellular process, developmental process, P53 signaling pathway, etc. At the single-cell level, the clusters of cells ranked were glandular and luminal cells c-24, glandular and luminal cells c-9, endothelial cells c-15, compared with the other cells. At the genetic level, promoter methylation levels of HOXB9 were significantly higher in tumors than in normal tissues. Furthermore, variations of HOXB9 were closely associated with overall survival (OS) and recurrence free survival (RFS) in EC patients (P &lt; 0.05). The agreement between univariate and multivariate Cox regression indicated that the results were more reliable. Stages III and IV, G2 and G3, tumor invasion ≥ 50%, mixed or serous histological type, age &gt; 60 years, and high expression of HOXB9 were risk factors strongly associated with OS in EC patients (P &lt; 0.05). Therefore, six factors were incorporated to construct a nomogram for survival prediction. Finally, we used the Kaplan-Meier (KM) curve, receiver operating characteristic (ROC) curve, and time-dependent ROC to assess predictive power of HOXB9. KM curve showed EC patients overexpressing HOXB9 had a worse OS. AUC of diagnostic ROC was 0.880. AUCs of time-dependent ROC were 0.602, 0.591, and 0.706 for 1-year, 5-year, and 10-year survival probabilities (P &lt; 0.001). Conclusions Our study provids new insights into the diagnosis and prognosis of HOXB9 in EC and constructs a model that can accurately predict the prognosis of EC.

HGF knockdown suppresses ovarian cancer malignancy: insights from a transient receptor potential-related gene model

Ovarian carcinoma (OV) is a prevalent gynecologic malignancy. While transient receptor potential (TRP) channels are substantially correlated with tumor growth, their role in OV remains unclear. This study therefore aims to construct a comprehensive TRP-related prognostic model and analyze its association with the cell infiltration and checkpoint expression. Based on transcriptomic data from public OV databases, TRP activity scores were calculated using single-sample gene set enrichment analysis (ssGSEA), and correlated gene modules were identified through Weighted Gene Co-expression Network Analysis (WGCNA). Functional enrichment analysis was performed to elucidate underlying biological pathways. A prognostic signature was developed via machine learning algorithms, and its clinical utility was validated through construction of a nomogram integrating key clinicopathological parameters. Comprehensive immune characterization was conducted to compare microenvironmental features between risk subgroups. Finally, functional assays including cell counting kit-8 (CCK-8), wound healing, and Transwell were employed to experimentally validate the role of a candidate gene in OV progression. Of the 21 co-expression modules identified, the brown module demonstrated the strongest positive correlation with TRP scores. Functional enrichment analysis revealed that TRP-related genes were predominantly involved in immune system pathways. Using the nine identified genes, a risk model was developed, and Riskscore was employed to categorize patients into high- and low-risk groups. Overall survival (OS) was notably higher for patients in the OV low-risk group than for those in the high-risk group. The nomogram's findings demonstrated that the Riskscore had an independent impact on prognosis. According to immunological characterization, the low-risk group had higher levels of cellular infiltration, including activated B cells and activated CD4 T cells. High-risk group had low expressions of immune checkpoint genes, including LAG3, CD274, and CD27. In vitro tests showed that HGF knockdown markedly reduced the viability, motility, and invasion of OV cells. The TRP-related gene signature constructed in this study predicts the prognosis and immune microenvironment status of OV patients, providing a new perspective for prognosis assessment and targeted therapy in OV.

Investigation of the mechanism by which FOXJ2 inhibits proliferation, metastasis and cell cycle progression of ovarian cancer cells through the PI3K/AKT signaling pathway

As one member of the Forkhead Box transcription factor, Forkhead Box J2 (FOXJ2) is involved in diverse cancers. At present, the specific role and mechanism of FOXJ2 in ovarian cancer (OC) have not been fully addressed, which allows us to fill the blank. Accordingly, the expression of FOXJ2 in OC cells and ovarian epithelial cells was quantified via real-time qPCR. Following the transfection, cell counting kit-8, Transwell, wound healing and flow cytometry assays were performed to measure the proliferation, metastasis, apoptosis and cell cycle of OC cells A2780 and HEY. Further, real-time qPCR and Western blotting were both employed for the quantification assays on the expression levels of FOXJ2 as well as phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT) (in both unphosphorylated and phosphorylated forms). Based on the results, FOXJ2 were highly-expressed in OC cells (P < 0.05). Silencing of FOXJ2 resulted in attenuated OC cell proliferation, reduced numbers of migrating and invading OC cells, decreased apoptotic capacity, and cell cycle arrest in G1/S phase (P < 0.05). In addition, the knockdown of FOXJ2 caused the downward trend on the phosphorylation level of both PI3K and AKT in OC cells (P < 0.05). The silencing of FOXJ2 could repress the growth and metastasis potentials and cause the cell cycle G1/S arrest of OC cells in vitro, which was possibly achieved via targeting the PI3K/AKT pathway.

SUGT1 is a prognostic biomarker and is associated with immune infiltrates in ovarian cancer

Ovarian cancer (OC) is a prevalent gynecological malignancy with a relatively dismal prognosis. The SGT1 homolog (SUGT1) protein, which interacts with heat shock protein 90 and is essential for the G1/S and G2/M transitions, was formerly thought to be a cancer promoter, but its precise role in OC remains unknown. We conducted a comprehensive bioinformatics analysis of SUGT1 expression in patients with OC compared with their normal controls, including the data from the cancer genome atlas (TCGA), genotype-tissue expression (GTEx) databases, gene ontology (GO) analysis, Kyoto Encylopedia of Genes and Genomes (KEGG) analysis, gene set enrichment analysis (GSEA), single sample gene set enrichment analysis (ssGSEA). In addition, Kaplan-Meier (KM) analysis, univariate and multivariate Cox analyses were applied to investigate the prognostic role of SUGT1 in ovarian cancer. Furthermore, we validated the expression of SUGT1 in OC and normal tissues through immunohistochemistry. SUGT1 was significantly overexpressed in OC than in normal tissues. In addition, the GO, KEGG and GSEA analysis revealed that SUGT1 was associated with the functions related to immunoglobulin complex, antigen binding, immunoglobulin receptor binding, among others. Besides, ssGSEA demonstrated a positive correlation between SUGT1 expression and the abundance of T central memory cells, natural killer cells, and T gamma delta cells, although it showed a negative association with activated dendritic cells, cytotoxic cells, T cells, and T helper 1 cells. Subsequently, KM survival analysis revealed that high SUGT1 expression indicated a shorter overall survival, disease specific survival and progression free interval in OC patients. Univariate and multivariate Cox regression revealed that SUGT1 could serve as an independent risk factor for prognosis of patients with OC. All these results of this study show that SUGT1 is an important molecular component in immune infiltration in OC and may have a new significant prognostic role in OC.

TCEB2/HIF1A signaling axis promotes chemoresistance in ovarian cancer cells by enhancing glycolysis and angiogenesis

Ovarian cancer is an extremely malignant gynaecological tumour with a poor patient prognosis and is often associated with chemoresistance. Thus, exploring new therapeutic approaches to improving tumour chemosensitivity is important. The expression of transcription elongation factor B polypeptide 2 (TCEB2) gene is reportedly upregulated in ovarian cancer tumour tissues with acquired resistance, but the specific mechanism involved in tumour resistance remains unclear. In this study, we found that TCEB2 was abnormally highly expressed in cisplatin-resistant tumour tissues and cells. TCEB2 silencing also inhibited the growth and glycolysis of SKOV-3/cisplatin (DDP) and A2780/DDP cells. We further incubated human umbilical vein endothelial cells (HUVECs) with culture supernatants from cisplatin-resistant cells having TCEB2 knockdown. Results revealed that the migration, invasion, and angiogenesis of HUVECs were significantly inhibited. Online bioinformatics analysis revealed that the hypoxia-inducible factor-1A (HIF-1A) protein may bind to TCEB2, and TCEB2 silencing inhibited SKOV-3/DDP cell growth and glycolysis by downregulating HIF1A expression. Similarly, TCEB2 promoted HUVEC migration, invasion, and angiogenesis by upregulating HIF1A expression. In vivo experiments showed that TCEB2 silencing enhanced the sensitivity of ovarian cancer nude mice to cisplatin and that TCEB2 knockdown inhibited the glycolysis and angiogenesis of tumour cells. Our findings can serve as a reference for treating chemoresistant ovarian cancer.

The prognostic value of calcium channel blockers usage for overall survival and recurrence-free survival in patients with endometrial cancer

To evaluate the prognosis for endometrial cancer (EC) patients who used calcium channel blockers (CCB) with hypertension and its predictive function. Patients diagnosed with EC who underwent surgery at our hospital between January 2014 and December 2023 were enrolled and divided into a training set and a validation set at a 2:1 ratio. Clinical characteristics and medical information were extracted from patient records. Predictive factors were assessed using univariate and multivariate analyses in the training set. ROC and DCA were employed to evaluate the predictive value of CCB in both the training and validation sets. Survival analysis was conducted to investigate function of antihypertensive drugs and calcium level. In the training set, univariate analysis showed that age, CA125, CCB use, tumor grade, FIGO stage, histological type, peritoneal cytology, lymph node metastasis, and lymph-vascular space invasion (LVSI) were significantly associated with overall survival (OS) and recurrence-free survival (RFS; all P < 0.05). After adjusting for confounders, CCB use remained independently predictive of improved OS (Model I: HR = 0.1, 95% CI: 0.0-0.4, P < 0.001; Model II: HR = 0.2, 95% CI: 0.1-0.5, P = 0.006) and RFS (Model I: HR = 0.2, 95% CI: 0.1-0.5, P < 0.001; Model II: HR = 0.2, 95% CI: 0.1-0.7, P = 0.009). Both CCB and calcium ion levels have significant impacts on the long-term survival of patients with hypertension. ROC and DCA demonstrated that incorporating CCB use significantly enhanced diagnostic accuracy for OS and RFS in both the training and validation sets. Survival analyses further supported these findings. This study suggests that hypertensive EC patients using CCB exhibit significantly improved OS and RFS prediction accuracy, with consistent results across training and validation cohorts.

CPA4 overexpression correlates with poor prognosis and tumor progression in endometrial cancer

The rise in endometrial cancer rates globally calls for advanced diagnostic methods and new biomarkers. CPA4, known for its role in cancer development, has not yet been studied in relation to endometrial cancer, making it a promising research avenue. We analyzed CPA4's mRNA expression using data from TCGA and GEO databases and validated these findings with 116 clinical samples through immunohistochemical analysis. The Ishikawa and Hec-1-A cell lines were used to examine CPA4's functionality. In addition, we conducted correlation analysis, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA), and survival analysis to understand CPA4's role in endometrial cancer prognosis. A nomogram model was developed for clinical prognostic predictions. CPA4 is significantly overexpressed in endometrial cancer, correlating with tumor progression and poor prognosis. Overexpression is linked to crucial functions, such as mitosis and cell cycle. Reducing CPA4 in cell lines inhibited tumor growth and spread. Kaplan-Meier plots and Cox regression analysis confirmed CPA4's significance in prognosis, with our predictive model showing high accuracy. CPA4 emerges as a vital biomarker for diagnosing and prognosing endometrial cancer, presenting a novel pathway for research and clinical application. The study highlights its potential as a clinical tool, paving the way for improved patient management and treatment strategies in endometrial cancer.