Oncology Research

SIK2 inhibitor SIC-19 enhances the sensitivity of PARP inhibitors in triple-negative breast cancers and pancreatic cancers

Circulating Tumor DNA in Cervical Cancer: Clinical Utility and Medico-Legal Perspectives

Cervical cancer related to human papillomavirus (HPV) is a leading cause of cancer-related mortality among women worldwide. Cancer cells release fragments of their DNA, known as circulating tumor DNA (ctDNA), which can be detected in bodily fluids. A PubMed search using the terms "ctHPV" or "circulating tumor DNA" and "cervical cancer", limited to the past ten years, identified 104 articles, complemented by hand-searching for literature addressing medico-legal implications. Studies were evaluated for relevance and methodological quality. Detection and characterization of circulating tumor HPV DNA (ctHPV DNA) have emerged as promising tools for assessing prognosis and disease recurrence in cervical cancer. Detection techniques include polymerase chain reaction (PCR), digital droplet PCR (ddPCR), and next-generation sequencing (NGS). This review summarizes current knowledge on ctHPV DNA in cervical cancer and explores its clinical and medico-legal implications, including management of discordant results, diagnostic errors, liability, and data protection compliance.

Magnetic melamine cross-linked polystyrene-alt-malic anhydride copolymer: Synthesis, characterization, paclitaxel delivery, cytotoxic effects on human ovarian and breast cancer cells

Due to systematic side effects, there is a growing interest in nanoparticle formulation of anticancer drugs. Here, we aimed to synthesize poly (styrene-alt-maleic anhydride) cross-linked by melamine (PSMA/Me) and coated with magnetite nanoparticles (MNPs) PSMA/Me/Fe Novel PSMA/Me was synthesized via free radical copolymerization, coated with Fe Characterization methods confirmed PSMA/Me copolymer formation. The results showed a significant encapsulation efficiency of 83%. The drug release analysis exhibited that PSMA/Me/Fe Our results indicated that PSMA/Me/Fe

Deubiquitinating Enzyme OTUDs: Focus on Cancers and Antiviral Response

miR-512-3p/RPS6KA2 Axis Regulates Cisplatin Resistance in Ovarian Cancer via Autophagy and Ferroptosis

Ribosomal protein S6 kinase A2 (RPS6KA2) has been identified as a potential prognostic biomarker in several cancers, including breast cancer, glioblastoma, and prostate cancer. However, its functional significance in ovarian cancer is not well characterized. This study was designed to explore the therapeutic relevance of modulating RPS6KA2 in the context of ovarian cancer, particularly in relation to cisplatin resistance. The expression levels of RPS6KA2 and key regulators involved in autophagy and ferroptosis were assessed using quantitative reverse transcription-PCR, immunofluorescence staining, immunohistochemistry, and western blotting. Prognostic associations were conducted using the Kaplan-Meier Plotter database. Autophagy flux assays and visualization of autophagosomes were performed to assess autophagy activity. Ferroptosis-related parameters, including intracellular iron content, glutathione (GSH) levels, reactive oxygen species (ROS) generation, and mitochondrial membrane potential, were measured to determine ferroptotic changes. Using ovarian cancer cell lines and clinical tissue samples, we demonstrated that RPS6KA2 expression was significantly downregulated in cisplatin-resistant cells and tissues compared to their sensitive counterparts. Low RPS6KA2 expression correlated with unfavorable patient outcomes and enhanced chemoresistance. Mechanistically, RPS6KA2 inhibited autophagy by modulating the phosphatidylinositol 3-kinase-protein kinase B-mammalian target of rapamycin (PI3K-AKT-mTOR) signaling pathway, which in turn increased sensitivity to cisplatin. Additionally, RPS6KA2 facilitated ferroptosis, contributing to its tumor-suppressive function. miR-512-3p was identified as a negative regulator of RPS6KA2, driving cisplatin resistance through suppression of RPS6KA2 expression. These results collectively indicate that targeting the miR-512-3p/RPS6KA2 regulatory axis may offer a novel and effective strategy for overcoming cisplatin resistance in ovarian cancer.

OTUD7B Stabilization by METTL14-Mediated m6A Methylation Drives HIF-1<b>α</b> Expression in Esophageal Squamous Cell Carcinoma

HE4 Might Participate in Extracellular Matrix Remodeling in Ovarian Cancer via Activation of Fibroblasts

High-grade serous ovarian cancer (HGSOC), the most common subtype of epithelial ovarian cancer (EOC), exhibits a mesenchymal phenotype characterized by fibrotic stroma and poor prognosis. Human epididymis protein 4 (HE4), a key diagnostic biomarker for ovarian cancer, is involved in fibrotic processes in several non-malignant diseases. Given the clinical significance of stromal fibrosis in HGSOC and the potential link between HE4 and fibrosis, this study aimed to investigate the role of HE4 in the formation of stromal fibrosis in HGSOC. A total of 126 patients with gynecological conditions were included and divided into normal, benign, and EOC groups. Tissue stiffness was quantitatively measured and analyzed for its correlation with clinicopathological features. We further investigated the correlation between tumor stiffness and the expression levels of HE4 and fibroblast activation markers (α-smooth muscle actin (α-SMA) and fibroblast activation protein (FAP)) in tumor tissues from 22 HGSOC patients. Ovarian cancer tissues showed significantly increased stiffness compared to benign/normal groups, showing positive correlation with serum HE4 levels. High-stiffness HGSOC tumors exhibited upregulated expression of HE4, α-SMA, FAP, and collagen I. rHE4 stimulated fibroblast activation and enhanced matrix contractility, whereas HE4 knockdown in cancer cells abrogated these pro-fibrotic effects. Our findings suggest that HE4 may facilitate ECM remodeling in HGSOC through promoting fibroblast activation and increasing collagen deposition.

Molecular Pathology of Ovarian Endometrioid Carcinoma: A Review

Ovarian endometrioid carcinoma (OEC) accounts for ~10% of epithelial ovarian cancers and displays broad morphologic diversity that complicates diagnosis and grading. Recent data show that the endometrial cancer molecular taxonomy (DNA polymerase epsilon, catalytic subunit [POLE]-ultramutated, mismatch repair-deficient [MMRd], p53-abnormal, no specific molecular profile [NSMP]) also applies to OEC, and that OEC is enriched for Lynch syndrome-associated tumors, supporting routine MMR testing. We aimed to synthesize contemporary evidence spanning epidemiology, histopathology and immunophenotype, diagnostic pitfalls and differential diagnosis, and to evaluate the clinical utility of The Cancer Genome Atlas (TCGA)-surrogate molecular classification for risk stratification; we also summarize implications for Lynch screening, genetic counseling, and therapeutic opportunities including immune checkpoint inhibitors and targeted approaches, with practical recommendations for diagnostic workflows. Integrating morphology with molecular classification refines diagnosis and prognostication: POLEmut/MMRd subsets generally have excellent outcomes and are candidates for de-escalation or immunotherapy, whereas p53abn/high-grade tumors carry a poorer prognosis and may warrant intensified management and trials of homologous recombination deficiency (HRD)-directed strategies; routine MMR immunohistochemistry (IHC) with reflex germline testing improves Lynch detection, and future priorities include prospective validation and multi-omics to refine NSMP and identify new targets.

Significance of CA125 Monitoring during Maintenance Treatment with Poly(ADP-Ribose) Polymerase Inhibitor in Ovarian Cancer after First-Line Chemotherapy: Multicenter, Observational Study

Monitoring of Cancer Antigen 125 (CA125) during ovarian cancer (OC) maintenance treatment with poly(ADP-ribose) polymerase inhibitors (PARPis) may be insufficient when using Gynecologic Cancer Intergroup (GCIG) biochemical progression criteria. This study aimed to evaluate the usefulness of CA125 monitoring in detecting OC recurrence during PARPis maintenance treatment. This multicenter retrospective cohort study included patients with primary OC who achieved complete or partial response after first-line platinum-based chemotherapy followed by PARPis maintenance treatment. Progression was defined using Response Evaluation Criteria in Solid Tumors (RECIST) and GCIG biochemical criteria. New biochemical progression definitions, based on CA125 nadir determined using receiver operating characteristic (ROC) curve analysis, were proposed. Concordance between radiological and biochemical progression was assessed. Of 142 patients, progression was detected in 54 (38.03%) and 29 (20.42%) using RECIST and GCIG criteria, respectively. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the GCIG criteria were 53.70% [95% confidence interval (CI): 39.61%-67.38%], 100.00% [95% CI:95.91%-100.00%], 100.00% [95%CI: 88.10%-100.00%] and 77.88% [95% CI: 72.54%-82.43%], respectively. A cut-off of 1.59× nadir achieved 88.90% sensitivity and 87.20% specificity [Area Under Curve (AUC): 91.10%, 95% CI: 84.70%-97.40%] with a false positive rate (FPR) of 12.67%. Defining biochemical progression as an increase in CA125 of ≥3× nadir achieved sensitivity, specificity, PPV, NPV, and FPR of 79.63% [95% CI: 66.47%-89.37%], 98.86% [95% CI: 93.83%-99.97%], 97.73% [95% CI: 85.91%-99.67%], 88.78% [95% CI: 82.35%-93.06%], and 1.14%, respectively. Diagnostic accuracy was higher using the ≥3× nadir criterion compared with GCIG definition (91.55% vs. 82.39%). GCIG biochemical progression criteria during PARPis maintenance treatment after first-line chemotherapy missed 46.3% of progressing patients. A new criterion-CA125 ≥3× nadir-improves sensitivity and NPV, while maintaining high specificity, offering a simple and practical approach for clinical implementation.

3<b></b>-Hydroxysterol <b>Δ</b>24-Reductase Promotes Ovarian Cancer Progression by Activating the TGF-<b></b>1/Smad2/3 Signaling Pathway

Ovarian cancer (OC) is a highly heterogeneous disease characterized by high metastatic potential and frequent recurrence. 3β-hydroxysterol Δ24-reductase (DHCR24) is closely associated with the progression of various malignant tumors, but its role in OC remains unexplored. This study is the first to systematically investigate the function of DHCR24 in OC and elucidate its mechanism in promoting OC progression, providing novel theoretical insights for targeted therapy. The expression of DHCR24 was evaluated in tissues using bioinformatics and clinical data; the impact of DHCR24 on the malignant behavior of OC was assessed through Database, clinical data, and immunohistochemical (IHC) analyses demonstrated that DHCR24 is upregulated in OC and correlates with poor outcomes. DHCR24 contributes to ovarian cancer progression by upregulating the TGF-β1 pathway, highlighting its potential as a therapeutic target in ovarian cancer.

Pyrimethamine Inhibits Human Ovarian Cancer by Triggering Lethal Mitophagy via Activating the p38/JNK/ERK Pathway

Ovarian cancer, a leading cause of gynecological malignancy-related mortality, is characterized by limited therapeutic options and a poor prognosis. Although pyrimethamine has emerged as a promising candidate demonstrating efficacy in treating various tumors, the precise mechanisms of its antitumor effects remain obscure. This study was specifically designed to investigate the mode of action underlying the antitumor effects of pyrimethamine in preclinical settings. The effects of pyrimethamine on cellular proliferation were meticulously assessed using both the cell counting kit 8 (CCK-8) assay and the colony formation assay, with the effects further confirmed in a murine model. A confocal microscope was utilized to monitor the dynamic alterations in mitochondria within ovarian cancer cells. Additionally, adenosine triphosphate (ATP) and reactive oxygen species (ROS) assays were conducted to measure mitochondrial damage induced by pyrimethamine in ovarian cancer cell lines. The mitochondrial membrane potential was assessed using fluorescent dyes as an indicator of mitochondrial functional status. Furthermore, transcriptome analysis and immunohistochemical techniques were employed to detect the impact of pyrimethamine on ovarian cancer cells. Our results demonstrated that pyrimethamine induced ovarian cancer cell death through mitochondrial dysfunction and lethal mitophagy. Transcriptome profiling analysis and Western blot demonstrated that activation of the p38/JNK/ERK signaling pathway was implicated in the process of pyrimethamine-induced mitophagy in ovarian cancer cells. Importantly, combination treatment with pyrimethamine and paclitaxel Altogether, these findings indicate that the antitumor effects of pyrimethamine result from the induction of lethal mitophagy via regulation of the p38/JNK/ERK pathway in ovarian cancer. Considering the low toxicity and high tolerance associated with pyrimethamine, it is suggested that pyrimethamine be evaluated in the treatment of ovarian cancer, either as a monotherapy or in combination with paclitaxel.

CYMP-AS1 Promotes Ovarian Cancer Progression by Enhancing the Intracellular Translocation of hnRNPM and Reducing the Stability of AXIN2 mRNA

Ovarian cancer (OC) is a representative malignancy of the female reproductive system, with a poor prognosis. Long non-coding RNAs (lncRNAs) crucially affect tumor development. This study aimed to identify lncRNAs that potentially participated in OC. LncRNA expression in cells and tissues was quantified using reverse transcription-quantitative PCR, while fluorescence This study identified a previously unreported lncRNA, CYMP-AS1, which exhibits increased expression in the cytoplasm of OC tissues and cells. Knockout of CYMP-AS1 reduced the OC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). CYMP-AS1 directly interacts with heterogeneous nuclear ribonucleoprotein M (hnRNPM), inducing its intracellular translocation and reducing the stability of Axis inhibition protein 2 (AXIN2) mRNA. This process ultimately elevated the expression of Wnt/β-catenin signaling pathway-related proteins. This study confirms CYMP-AS1 as a novel biomarker in OC progression and suggests that the CYMP-AS1/hnRNPM/AXIN2 axis may offer an innovative strategy for OC treatment.

Clinical and Functional Characterization of PDE1A as a Wnt/<b>β</b>-Catenin-Linked Biomarker of Progression and Platinum Resistance in Epithelial Ovarian Cancer

Phosphodiesterase 1A (PDE1A) regulates intracellular cyclic nucleotide signaling and has been implicated in tumor progression, but its clinical relevance and functional role in epithelial ovarian cancer (EOC), particularly in relation to the response to platinum remain unclear. This study aimed to evaluate the clinical significance of PDE1A in EOG and to clarify its functional role in tumor progression and response to platinum-based chemotherapy. PDE1A mRNA and protein levels were analyzed using public databases, RNA sequencing, and immunohistochemistry. Correlations between PDE1A expression, clinicopathological features, and prognosis were assessed. Functional roles were investigated in ovarian cancer cell lines. PDE1A was significantly overexpressed in EOC tissues compared with that in normal ovarian epithelial tissues. Overexpression correlated with advanced International Federation of Gynecology and Obstetrics (FIGO) stage, poor tumor grade, and reduced response to platinum-based chemotherapy. High PDE1A levels were linked to worse disease-free survival and overall survival, and multivariate analysis confirmed PDE1A as an independent prognostic factor. To elucidate its functional role, we performed In conclusion, our findings identify PDE1A as a Wnt/β-catenin-linked biomarker of tumor progression and platinum resistance in EOC and provide a biological rationale for further investigation of PDE1A-targeted strategies in preclinical models.

A novel isoxazole compound CM2-II-173 inhibits the invasive phenotype of triple-negative breast cancer cells

Invasion and metastasis are important hallmarks of breast cancer and are the leading cause of patient mortality. Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer characterized by a poor prognosis and a lack of effective targeted therapies. The present study investigated the inhibitory effect of a novel FTY720 derivative on the invasive phenotype of TNBC cells. Here, we showed that a novel compound with an isoxazole ring, 4-(3-Decylisoxazol-5-yl)-1-hydroxy-2-(hydroxymethyl)butan-2-aminium chloride (CM2-II-173), significantly inhibited invasiveness of MDA-MB-231 TNBC cells. Expression of matrix metalloproteinase (MMP)-9 and invasiveness of MCF10A normal breast cells induced by sphingosine-1-phosphate (S1P) were reduced by CM2-II-173 treatment. Activations of pMEK1, pAkt, pERK, and p38 MAPK by S1P were inhibited by treatment with CM2-II-173. Proliferation and anchorage-independent growth of MDA-MB-231 TNBC cells were significantly decreased by CM2-II-173. CM2-II-173 efficiently induced apoptosis in MDA-MB-231 TNBC cells. CM2-II-173 significantly inhibited invasive phenotypes of breast, liver, prostate, and ovarian cancer cells. CM2-II-173 exhibited a more potent effect on the invasiveness of MDA-MB-231 TNBC cells compared to FTY720. Taken together, this study demonstrated that CM2-II-173 has the potential to be a lead compound that can inhibit cancer progression of not only TNBC cells, but also of liver, prostate, and ovarian cancer cells.

PPARα activator irbesartan suppresses the proliferation of endometrial carcinoma cells via SREBP1 and ARID1A

Endometrial carcinoma (EMC) is associated with obesity; however, the underlying mechanisms have not yet been elucidated. Peroxisome proliferator-activated receptor alpha (PPARα) is a nuclear receptor that is involved in lipid, glucose, and energy metabolism. PPARα reportedly functions as a tumor suppressor through its effects on lipid metabolism; however, the involvement of PPARα in the development of EMC remains unclear. The present study demonstrated that the immunohistochemical expression of nuclear PPARα was lower in EMC than in normal endometrial tissues, suggesting the tumor suppressive nature of PPARα. A treatment with the PPARα activator, irbesartan, inhibited the EMC cell lines, Ishikawa and HEC1A, by down-regulating sterol regulatory element-binding protein 1 (SREBP1) and fatty acid synthase (FAS) and up-regulating the tumor suppressor genes p21 and p27, antioxidant enzymes, and AT-rich interaction domain 1A (ARID1A). These results indicate the potential of the activation of PPARα as a novel therapeutic approach against EMC.

Omics sciences for cervical cancer precision medicine from the perspective of the tumor immune microenvironment

Immunotherapies have demonstrated notable clinical benefits in the treatment of cervical cancer (CC). However, the development of therapeutic resistance and diverse adverse effects in immunotherapy stem from complex interactions among biological processes and factors within the tumor immune microenvironment (TIME). Advanced omic technologies offer novel insights into a more expansive and thorough layer of the TIME. Furthermore, integrating multidimensional omics within the frameworks of systems biology and computational methodologies facilitates the generation of interpretable data outputs to characterize the clinical and biological trajectories of tumor behavior. In this review, we present advanced omics technologies that utilize various clinical samples to address scientific inquiries related to immunotherapies for CC, highlighting their utility in identifying metastasis dissemination, recurrence risk, and therapeutic resistance in patients treated with immunotherapeutic approaches. This review elaborates on the strategy for integrating multi-omics data through artificial intelligence algorithms. Additionally, an analysis of the obstacles encountered in the multi-omics analysis process and potential avenues for future research in this domain are presented.

LncRNA AFAP1-AS1 exhibits oncogenic characteristics and promotes gemcitabine-resistance of cervical cancer cells through miR-7-5p/EGFR axis

Drug resistance is the main factor contributing to cancer recurrence and poor prognosis. Exploration of drug resistance-related mechanisms and effective therapeutic targets are the aim of molecular targeted therapy. In our study, the role of long non-coding RNA (lncRNA) AFAP1-AS1 in gemcitabine resistance and related mechanisms were explored in cervical cancer cells. Gemcitabine-resistant cervical cancer cell lines HT-3-Gem and SW756-Gem were constructed using the gemcitabine concentration gradient method. The overall survival rates and recurrence-free survival rates were evaluated by Kaplan-Meier analysis. The interaction was verified through a Dual-luciferase reporter gene assay and a Biotinylated RNA pull-down assay. Cell proliferation ability was assessed through methyl-thiazolyl-tetrazolium (MTT), soft agar, and colony formation experiments. Cell cycle and apoptosis were detected by flow cytometry. Up-regulation of AFAP1-AS1 in cervical cancer predicted a poor prognosis. Besides, patients in the gemcitabine-resistance group had higher levels of AFAP1-AS1 than the gemcitabine-sensitive group. AFAP1-AS1 promoted tumor growth and induced gemcitabine tolerance of cervical cancer cells. In addition, AFAP1-AS1 mediated epidermal growth factor receptor (EGFR) expression by serving as a molecular sponge for microRNA-7a-5p (miR-7-5p). This present study also proved that the knockdown of EGFR or overexpression of miR-7a-5p abolished the accelerative role of AFAP1-AS1 overexpression in cancer progression and gemcitabine tolerance. In general, the AFAP1-AS1/miR-7-5p/EGFR axis was tightly related to the progression and gemcitabine tolerance of cervical cancer, providing potential targets for the management of cervical cancer.

Transformer 2β regulates the alternative splicing of cell cycle regulatory genes to promote the malignant phenotype of ovarian cancer

Late-stage ovarian cancer (OC) has a poor prognosis and a high metastasis rate, but the underlying molecular mechanism is unclear. RNA binding proteins (RBPs) play important roles in posttranscriptional regulation in the contexts of neoplasia and tumor metastasis. In this study, we explored the molecular functions of a canonical RBP, Transformer 2β homolog (TRA2B), in cancer cells. TRA2B knockdown in HeLa cells and subsequent whole-transcriptome RNA sequencing (RNA-seq) analysis revealed the TRA2B-regulated alternative splicing (AS) profile. We disrupted TRA2B expression in epithelial OC cells and performed a series of experiments to confirm the resulting effects on OC cell proliferation, apoptosis and invasion. TRA2B-regulated AS was tightly associated with the mitotic cell cycle, apoptosis and several cancer pathways. Moreover, the expression of hundreds of genes was regulated by TRA2B, and these genes were enriched in the functions of cell proliferation, cell adhesion and angiogenesis, which are related to the malignant phenotype of OC. By integrating the alternatively spliced and differentially expressed genes, we found that AS events and gene expression were regulated independently. We then explored and validated the oncogenic functions of TRA2B by knocking down its expression in OC cells. The high TRA2B expression was associated with poor prognosis in patients with OC. In ovarian tissue, TRA2B expression showed a gradual increasing trend with increasing malignancy. We demonstrated the important roles of TRA2B in ovarian neoplasia and aggressive OC behaviors and identified the underlying molecular mechanisms, facilitating the targeted treatment of OC.

System analysis based on the T cell exhaustion‑related genes identifies CD38 as a novel therapy target for ovarian cancer

Ovarian cancer (OV) is highly heterogeneous tumor with a very poor prognosis. Studies increasingly show that T cell exhaustion is prognostically relevant in OV. The aim of this study was to dissect the heterogeneity of T cell subclusters in OV through single cell transcriptomic analysis. The single RNA-sequencing (scRNA-seq) data of five OV patients were analyzed, and six major cell clusters were identified after threshold screening. Further clustering of T cell-associated clusters revealed four subtypes. Pathways related to oxidative phosphorylation, G2M checkpoint, JAK-STAT and MAPK signaling were significantly activated, while the p53 pathway was inhibited in the CD8+ exhausted T cells. The standard marker genes of CD8+ T cell exhaustion were screened to develop a T-cell related gene score (TRS) based on random forest plots in TCGA cohort. The patients with low TRS have better prognosis compared to the patients with high TRS in both TCGA and GEO. In addition, most genes included in the TRS showed significant differences in expression levels between the high- and low-risk groups. Immune cell infiltration was analyzed using the MCPcounter and xCell algorithms, which revealed significant differences between the two risk groups, indicating that the different prognoses may stem from the respective immune landscapes. In addition, CD38 knockdown in OV cell lines increased apoptosis and inhibited invasion

LncRNA CACNA1G-AS1 up-regulates FTH1 to inhibit ferroptosis and promote malignant phenotypes in ovarian cancer cells

Previous study revealed that ferritin heavy chain-1 (FTH1) could regulate ferritinophagy and affect intracellular Fe

Drug repositioning of disulfiram induces endometrioid epithelial ovarian cancer cell death via the both apoptosis and cuproptosis pathways

Various therapeutic strategies have been developed to overcome ovarian cancer. However, the prognoses resulting from these strategies are still unclear. In the present work, we screened 54 small molecule compounds approved by the FDA to identify novel agents that could inhibit the viability of human epithelial ovarian cancer cells. Among these, we identified disulfiram (DSF), an old alcohol-abuse drug, as a potential inducer of cell death in ovarian cancer. Mechanistically, DSF treatment significantly reduced the expression of the anti-apoptosis marker B-cell lymphoma/leukemia-2 (Bcl-2) and increase the expression of the apoptotic molecules Bcl2 associated X (Bax) and cleaved caspase-3 to promote human epithelial ovarian cancer cell apoptosis. Furthermore, DSF is a newly identified effective copper ionophore, thus the combination of DSF and copper was used to reduce ovarian cancer viability than DSF single treatment. Combination treatment with DSF and copper also led to the reduced expression of ferredoxin 1 and loss of Fe-S cluster proteins (biomarkers of cuproptosis).

PRPF6 promotes metastasis and paclitaxel resistance of ovarian cancer via SNHG16/CEBPB/GATA3 axis

Metastasis and paclitaxel (PTX) resistance are the main reason for the poor prognosis of ovarian cancer (OC). Evidence showed that RNA-binding proteins (RBPs) and long noncoding RNAs (lncRNAs) can modulate post-transcriptional regulation. The aim of this study was to determine the relationship among RBP, lncRNA and OC and to further guide clinical therapy. Immunohistochemistry revealed that pre-mRNA processing factor 6 (PRPF6) was upregulated in OC chemoresistant tissues and was closely related to advanced (Federation of International of Gynecologists and Obstetricians) FIGO stages and chemo-resistance. PRPF6 promoted progression, and PTX resistance

Comprehensive analysis of the expression and prognosis for APOE in malignancies: A pan-cancer analysis

Apolipoprotein E (

Comprehensively analyzing the genetic alterations, and identifying key genes in ovarian cancer

Though significant improvements have been made in the treatment methods for ovarian cancer (OC), the prognosis for OC patients is still poor. Exploring hub genes associated with the development of OC and utilizing them as appropriate potential biomarkers or therapeutic targets is highly valuable. In this study, the differentially expressed genes (DEGs) were identified from an independent GSE69428 Gene Expression Omnibus (GEO) dataset between OC and control samples. The DEGs were processed to construct the protein-protein interaction (PPI) network using STRING. Later, hub genes were identified through Cytohubba analysis of the Cytoscape. Expression and survival profiling of the hub genes were validated using GEPIA, OncoDB, and GENT2. For exploring promoter methylation levels and genetic alterations in hub genes, MEXPRESS and cBioPortal were utilized, respectively. Moreover, DAVID, HPA, TIMER, CancerSEA, ENCORI, DrugBank, and GSCAlite were used for gene enrichment analysis, subcellular localization analysis, immune cell infiltration analysis, exploring correlations between hub genes and different diverse states, lncRNA-miRNA-mRNA co-regulatory network analysis, predicting hub gene-associated drugs, and conducting drug sensitivity analysis, respectively. In total, 8947 DEGs were found between OC and normal samples in GSE69428. After STRING and Cytohubba analysis, 4 hub genes including TTK (TTK Protein Kinase), (BUB1 mitotic checkpoint serine/threonine kinase B) BUB1B, (Nucleolar and spindle-associated protein 1) NUSAP1, and (ZW10 interacting kinetochore protein) ZWINT were selected as the hub genes. Further, it was validated that these 4 hub genes were significantly up-regulated in OC samples compared to normal controls, but overexpression of these genes was not associated with overall survival (OS). However, genetic alterations in those genes were found to be linked with OS and disease-free (DFS) survival. Moreover, this study also revealed some novel links between TTK, BUB1B, NUSAP1, and ZWINT overexpression and promoter methylation status, immune cell infiltration, miRNAs, gene enrichment terms, and various chemotherapeutic drugs. Four hub genes, including TTK, BUB1B, NUSAP1, and ZWINT, were revealed as tumor-promotive factors in OC, having the potential to be utilized as novel biomarkers and therapeutic targets for OC management.

Galectins dysregulation: A way for cancer cells to invade and pervade

Galectins are sticky molecules that bind to β-galactoside. Their interactions render them essential players in many cellular processes. The imbalance of galectin expression was reported in many diseases. In cancer, galectins interact with the extracellular matrix, evade the immune system, and potentially have broad interactions with blood components. In the last ten years, since 2010, we did focus on galectin research in different cancer types. Our findings showed an interaction between cancer cells and erythrocytes via galectin-4. Moreover, we found that upregulation of galectins was associated with lymph node metastasis in ovarian cancers. Hence, with this, we shortly review some important aspects of galectins and their potential importance in more profound understanding of cancer progression and the field of cancer biomarkers.

The regulatory role of <i>ZFAS1/</i>miRNAs/mRNAs axis in cancer: a systematic review

FOXR2 in cancer development: emerging player and therapeutic opportunities

Adjuvant Chemotherapy Necessity in Stage I Ovarian Endometrioid Carcinoma: A SEER-Based Study Verified by Single-Center Data and Meta-Analysis

The benefit of adjuvant chemotherapy for stage I ovarian endometrioid carcinoma (OEC) remains controversial. Hence, the study sought to explore its value in stage I OEC patients. Stage I OEC patients (1988-2018) were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate Cox analysis was used to control confounders. Logistic regression was used to explore factors associated with adjuvant chemotherapy. Cox regression analysis and Kaplan-Meier curves were used to assess the survival benefits. Single-center clinical data and meta-analysis following PRISMA guidelines provided external validation. Adjuvant chemotherapy correlated with improved survival (Hazard Ratio (HR): 0.860, Adjuvant chemotherapy confers survival benefits for stage IC patients, particularly those without lymphadenectomy.

Deciphering resistance mechanisms and novel strategies to overcome drug resistance in ovarian cancer: a comprehensive review

Ovarian cancer is among the most lethal gynecological cancers, primarily due to the lack of specific symptoms leading to an advanced-stage diagnosis and resistance to chemotherapy. Drug resistance (DR) poses the most significant challenge in treating patients with existing drugs. The Food and Drug Administration (FDA) has recently approved three new therapeutic drugs, including two poly (ADP-ribose) polymerase (PARP) inhibitors (olaparib and niraparib) and one vascular endothelial growth factor (VEGF) inhibitor (bevacizumab) for maintenance therapy. However, resistance to these new drugs has emerged. Therefore, understanding the mechanisms of DR and exploring new approaches to overcome them is crucial for effective management. In this review, we summarize the major molecular mechanisms of DR and discuss novel strategies to combat DR.

TGF-β-regulated different iron metabolism processes in the development and cisplatin resistance of ovarian cancer

The impact of different iron metabolism processes (DIMP) on ovarian cancer remains unclear. In this study, we employed various gene chips and databases to investigate the role of DIMP in the initiation and development of ovarian cancer. cBioPortal was used to determine mutations in DIMP-associated genes in ovarian cancer. Kaplan-Meier plotter was used to examine the influence of DIMP on the prognosis of ovarian cancer. By analyzing 1669 serous ovarian cancer cases, we identified a range of mutations in iron metabolism genes, notably in those coding for the transferrin receptor (19%), melanotransferrin (19%), and ceruloplasmin (10%) in the iron import process, and glucose-6-phosphate isomerase (9%), hepcidin antimicrobial peptide (9%), metal regulatory transcription factor 1 (8%), and bone morphogenetic protein 6 (8%) in the iron regulation process. Compared to the unaltered group, the group with gene alterations exhibited a higher tumor mutation burden count (43

Pharmacological methods for ovarian function and fertility preservation in women with cancer: A literature review

LncRNA PCGEM1 facilitates cervical cancer progression via miR-642a-5p/KIF5B axis

At present, the role of many long non-coding RNAs (lncRNAs) as tumor suppressors in the formation and development of cervical cancer (CC) has been studied. However, lncRNA prostate cancer gene expression marker 1 (PCGEM1), whose high expression not only aggravates ovarian cancer but also can induce tumorigenesis and endometrial cancer progression, has not been studied in CC. The objective of this study was to investigate the expression and the underlying role of PCGEM1 in CC. The relative expression of PCGEM1 in CC cells was detected by real-time PCR. After the suppression of PCGEM1 expression by shRNA, the changes in the proliferation, migration, and invasion capacities were detected via CCK-8 assay, EdU assay, and colony formation assay wound healing assay. Transwell assay and the changes in expressions of epithelial-to-mesenchymal transition (EMT) markers were determined by western blot and immunofluorescence. The interplay among PCGEM1, miR-642a-5p, and kinesin family member 5B (KIF5B) was confirmed by bioinformatics analyses and luciferase reporter assay. Results showed that PCGEM1 expressions were up-regulated within CC cells. Cell viabilities, migration, and invasion were remarkably reduced after the suppression of PCGEM1 expression by shRNA in Hela and SiHa cells. N-cadherin was silenced, but E-cadherin expression was elevated by sh-PCGEM1. Moreover, by sponging miR-642a-5p in CC, PCGEM1 was verified as a competitive endogenous RNA (ceRNA) that modulates KIF5B levels. MiR-642a-5p down-regulation partially rescued sh-PCGEM1's inhibitory effects on cell proliferation, migration, invasion, and EMT process. In conclusion, the PCGEM1/miR-642a-5p/KIF5B signaling axis might be a novel therapeutic target in CC. This study provides a research basis and new direction for targeted therapy of CC.

Drug discovery in advanced and recurrent endometrial cancer: Recent advances

Endometrial cancer is the most common gynecologic cancer diagnosed in the United States and mortality is on the rise. Advanced and recurrent endometrial cancer represents a treatment challenge as historically there have been limited therapeutic options for patients. In the last several years, multiple practice-changing clinical trials have led to significant improvements in the treatment landscape. This review will cover updates in the treatment and management of advanced and recurrent endometrial cancer with a focus on novel therapeutics, such as anti-PD-L1 and PD-1 inhibitors, poly ADP-ribose polymerase (PARP) inhibitors, antibody-drug conjugates, and hormonal therapy.