Journal

Science Progress

Papers (18)

Investigating miRNA-driven DNA methylation: Statistical evidence of gene-specific modulation

Objective DNA methylation is a key regulator of gene expression and plays a crucial role in cancer development. However, the mechanisms driving gene-specific methylation remain unclear. This study investigates the role of microRNAs (miRNAs) in regulating promoter methylation of specific genes, aiming to uncover miRNA-driven modulation of gene methylation in cancer. Methods We analyzed data from the Cancer Cell Line Encyclopedia (CCLE) database, comprising 813 cell lines. Spearman's rank correlation was performed between the expression levels of 734 miRNAs and the methylation levels of 20,587 genes, focusing on CpG islands in promoter regions. Linear regression analysis was used to validate the relationship between selected miRNAs and gene clusters. Bioinformatics screening identified statistically significant miRNA-gene pairs involved in promoter methylation. Results The analysis revealed 25 target genes whose promoter methylation was significantly associated with the expression of four miRNAs (hsa-miR-200a, hsa-miR-200b, hsa-miR-200c, and hsa-miR-141). These correlations were most pronounced in colorectal, gastric, lung, and ovarian cancers. Notably, cancer-related genes such as ST14, OVOL1, and EPCAM were identified as targets, supporting the hypothesis that miRNAs regulate promoter methylation in these genes. Conclusion Our findings suggest that specific miRNAs induce promoter methylation in cancer-related genes, thereby influencing gene expression. This study expands our understanding of the role of miRNAs in tumor development and highlights the potential of miRNA-based therapies in cancer treatment. As this is a computational study, further experimental validation is required to confirm the proposed regulatory mechanisms.

Aetiology and management of persistent withdrawal occlusion in venous ports in oncology patients

Introduction: Persistent withdrawal occlusion (PWO) is a specific catheter malfunction characterized by the inability to withdraw blood through the device. The most common cause of PWO in ports is the presence of a fibroblastic sleeve (FS). If malfunction occurs, medication can be applied incorrectly with the increased risk of complications. Methods: One hundred seventy-seven cases of PWO in venous ports were managed. We focused on evaluating the cause of PWO, the frequency of occurrence of FS, and the options to address the malfunction. The patients underwent fluoroscopy with a contrast agent administration. Mechanical disruption (MD) with a syringe of saline using the flush method was used; in case of its failure, subsequent administration of a lock solution with taurolidine and urokinase, or low-dose thrombolysis with alteplase was indicated. Demographic data were compared with a control group. Results: A significantly higher proportion of female patients was found in the cohort of patients with PWO (80.3% vs 66.3%, p = 0.004), dominantly patients with ovarian cancer (12.8% vs 4.8%, p = 0.022). No effect of the cannulated vein or the type of treatment on the incidence of PWO was demonstrated. The presence of FS was verified in 70% of cases. MD with a syringe was successful in 53.5% of cases. A significantly shorter time to referral (3 weeks) was demonstrated with successful management. The overall success rate of achieving desobliteration by MD alone or in combination with a thrombolytic (urokinase or alteplase) administration was 97.4%. Conclusion: We created a method for resolving PWO using MD +/- application of thrombolytics with 97.4% success rate. Current evidence showed that FS is not likely to be affected by thrombolytic drugs; however, we have ascertained an effect of these drugs, proposing a hypothesis of microthrombotic events at the tip of the catheter if fibroblastic sleeve is present.

Coexistence of uterine adenosarcoma and endometrioid endometrial carcinoma: A case report and literature review

Uterine adenosarcoma coexisting with endometrial carcinoma is a very rare disease. Herein, we reported the case of uterine adenosarcoma coexisting with endometrioid endometrial carcinoma. Transvaginal ultrasound, computed tomography, and magnetic resonance imaging examinations all indicated a space-occupying lesion in the uterine cavity, and initially was considered endometrial carcinoma. Subsequently, total hysterectomy combined with bilateral salpingo-oophorectomy, pelvic lymphadenectomy, and para-aortic lymphadenectomy were performed. The coexistence of uterine adenosarcoma and endometrioid endometrial carcinoma was histologically confirmed postoperatively. The patient recovered well after surgery and was discharged on postoperative day 7. At a follow-up examination 10 months after surgery, we found no evidence of discomforting symptoms and recurrence or metastasis. Since the coexistence of uterine adenosarcoma and endometrial carcinoma is rare, it is easy to be overlooked the presence of uterine adenosarcoma on imaging or morphology, and thus be misdiagnosed as a more common disease, namely endometrial carcinoma. Observing the cystic structure within the lesion on magnetic resonance imaging is helpful for the diagnosis of uterine adenosarcoma. This article summarizes the imaging characteristics, clinicopathological features, molecular correlation, treatment, and prognosis of the disease.

Virome capture sequencing for comprehensive HPV genotyping in cervical samples

Objective This study aims to explore HPV genotyping in the cervical specimen using VirCapSeq by comparing the results with the reverse blot hybridization assay (REBA). Methods A secondary cross-sectional data of HPV genotypes in 35 cervical specimens was obtained from VirCapSeq and REBA methods. The .FASTQ files were downloaded from the NCBI Sequence Read Archive (SRA) (accession number PRJNA766412) and HPV genotyping was bioinformatically analyzed by mapping the sequences to the PaVE database. HPV genotypes detected by REBA and NGS were compared. All specimens were stratified by histology into cervical intraepithelial neoplasia grades 1 (CIN1) and 2/3 (CIN2/3). Results NGS via VirCapSeq detected HPV DNA in 100% of the samples, whereas the REBA (hybridization-based) assay diagnosed HPV DNA in 85.71%. While the limitation of the conventional methods for HPV genotyping is the use of primers or probes, NGS detected a broader range. The results showed that mixed infections were detected in all samples by NGS, with HPV16 and HPV52 being the most abundant genotypes. Conclusions HPV genome abundance, coverage, and diversity were associated with detection discrepancies between the methods, highlighting the enhanced sensitivity and diagnostic capabilities of NGS. These findings underscore the potential of NGS technologies for comprehensive HPV genotyping, advancing cervical cancer screening, and epidemiological studies. Future research should address cost barriers and expand cohort sizes to validate these findings.

Effects of chemoradiotherapy on plasma oncogenic miRNAs as biomarkers in cervical cancer patients: A prospective observational study

Background Cervical cancer (CC) is a leading cause of death among women worldwide, predominantly driven by high-risk human papillomavirus infection. MicroRNAs (miRNAs) regulate gene expression and may serve as noninvasive biomarkers for diagnosis, prognosis, and treatment monitoring in CC. Objective This study aimed to identify circulating miRNAs linked to HPV-related CC and evaluate their potential as biomarkers for prognosis and response to concurrent chemoradiotherapy (CRT). Methods In this prospective study, plasma samples from 36 CC patients were collected before and after treatment. Five miRNAs (hsa-miR-1-3p, hsa-miR-10a-5p, hsa-miR-34a-5p, hsa-miR-34c-5p, and hsa-miR-409-3p) were selected via literature review and pathway analysis. miRNA levels were quantified by quantitative polymerase chain reaction and normalized to hsa-miR-16. Associations with clinicopathological features and survival were analyzed statistically. Results Pathway analysis confirmed the involvement of selected miRNAs in cancer and HPV-related pathways, including PI3K-Akt and MAPK signaling. Post-CRT, significant downregulation of hsa-miR-34a-5p, hsa-miR-34c-5p, and hsa-miR-409-3p was observed ( p  < 0.05), indicating their potential as treatment response markers. Baseline hsa-miR-1-3p expression was significantly associated with Federation of Gynecology and Obstetrics stage ( p  = 0.043). No miRNAs showed significant associations with overall survival. Conclusions Circulating miRNAs, especially hsa-miR-34a-5p, hsa-miR-409-3p, and hsa-miR-34c-5p hold promise as noninvasive biomarkers for monitoring treatment efficacy in CC. Larger studies are needed to validate these findings and clarify their prognostic value.

AI-driven patient-centered care: A digital transformation framework for gynecologic cancer genetic counseling

Objectives This study evaluates artificial intelligence (AI) reasoning capabilities in gynecologic cancer genetic counseling, comparing the performance of ChatGPT and DeepSeek models to guide patient-centered AI implementation in clinical genetics. Methods Using 40 National Comprehensive Cancer Network-aligned counseling scenarios, we conducted blinded dual-oncologist evaluations of two large language models. Methodological rigor included model anonymization, a pre-calibrated scoring framework, and validated metrics (Global Quality Scale and Patient Education Materials Assessment Tool) assessing informational coherence, understandability, and actionability. Results DeepSeek demonstrated superior informational breadth (mean character difference: −609.0, p  < .0001) and visual communication (diagram integration, p  < .01), with 49-fold greater probability in recommending clear and actionable actions ( p  < .01, OR = 49.0). ChatGPT excelled in concise summarization (22% faster response generation, p  = .013). Conclusion Strategic AI model selection—leveraging DeepSeek's visually-rich, structured educational approach for complex information, and ChatGPT's concise, rapid summarization for efficient communication—enhances patient-centered genetic education when combined with clinician oversight. This framework supports healthcare's digital transformation by optimizing human-AI collaboration in hereditary cancer care.

Predicting complete response to concurrent chemoradiotherapy in locally advanced cervical squamous cell carcinoma using multi-sequence MRI data and a 2.5D deep learning algorithm integrated with crossformer model

Objective Despite advances in prevention, cervical cancer remains a serious global health issue. Concurrent chemoradiation is the standard treatment for locally advanced squamous cell carcinoma, yet 20–30% of patients develop persistent cervical cancer due to incomplete response, resulting in poor outcomes. This study aims to develop a predictive model for persistent cervical cancer in patients with locally advanced cervical squamous cell carcinoma following concurrent chemoradiation therapy, leveraging pretreatment multisequence magnetic resonance imaging data and advanced deep learning techniques. Methods This retrospective study included 259 patients with locally advanced cervical squamous cell carcinoma who underwent concurrent chemoradiation therapy at two centres. Four magnetic resonance imaging sequences were used to generate 2.5D data. A deep learning model incorporating Crossformer was developed and compared with radiomics and clinical models. Model performance was evaluated using receiver operating characteristic curves, calibration curves, and decision curve analysis. Results CrossFormer model outperformed the traditional convolutional neural network models in slice-level analysis across all cohorts, achieving an area under the curve of 0.775 in the test cohorts. The deep learning model achieved high predictive accuracy, with area under the curves of 0.884, 0.833, and 0.814 in the training, validation, and test cohorts, respectively, outperforming both the clinical and radiomics models. Combining clinical features with the deep learning model further improved performance, yielding area under the curves of 0.914, 0.868, and 0.839 in the respective cohorts. Conclusion The developed model, utilizing 2.5D multi-sequence magnetic resonance imaging data and the deep learning technology that incorporated Crossformer, demonstrated strong predictive performance for persistent cervical cancer in patients with locally advanced cervical squamous cell carcinoma following concurrent chemoradiation therapy. This approach offers a promising and clinically applicable tool for treatment decision-making.

APLN: A potential novel biomarker for cervical cancer

Apelin (APLN) is recently demonstrated a direct association with many malignant diseases. However, its effects on cervical cancer remain unclear. This study therefore aims to evaluate the association between APLN expression and cervical cancer using publicly available data from The Cancer Genome Atlas (TCGA). The Pearson χ2 test and Fish exact test, as well as logistic regression, were used to evaluate the relationship between clinicopathological factors in cervical cancer and the expression of APLN. Additionally, the Cox regression and Kaplan-Meier methods were conducted to analyze the Overall Survival (OS) of cervical cancer patients in TCGA. Finally, gene set enrichment analysis (GSEA) was performed to establish its biological functions. High expression of APLN in cervical cancer was significantly associated with a more advanced clinical stage (OR = 1.91 (1.21–3.05) for Stage II, Stage III, and Stage IV vs Stage I, p = 0.006). Additionally, it was associated with poor outcome after primary therapy (OR = 2.14 (1.03–4.59) for Progressive Disease (PD), Stable Disease (SD), and Partial Response (PR) vs Complete Remission (CR), p = 0.045) and high histologic grade (OR = 1.67 (1.03–2.72) for G3 and G4 vs G1 and G2, p = 0.037). Moreover, multivariate analysis showed that high expression of APLN was associated with a shorter OS. GSEA demonstrated that six KEGG pathways, including PPAR signaling, ECM-receptor interaction, focal adhesion, MAPK signaling, TGF-beta signaling, and Gap junction pathways were differentially enriched in the high expression APLN phenotype. The recent study suggests that APLN plays an important role in the progression of cervical cancer and might be a promising prognostic biomarker of the disease.

The role of radiotherapy in neuroendocrine cervical cancer: SEER-based study

Background: There are few randomised prospective data or guidelines for the treatment of neuroendocrine cervical cancer (NECC). In addition, the role of radiotherapy (RT) in NECC remains controversial. We used the Surveillance Epidemiology and End Results (SEER) database to investigate the role of RT for the treatment of NECC. Particular attention was paid to the different role of RT in patients with or without a metastasis (M1 or M0). Methods: The SEER database was queried for studies on NECC. We limited the year of diagnosis to the years 2000 to 2015. A Pearson’s two-sided Chi-squared test, the Kaplan–Meier method and Cox regression analysis models were used for statistical analyses. The overall survival (OS) was studied for the overall group and between-subgroup groups. Results: NECC was an aggressive disease with a mean OS of only 46.3 months (range of 0–196 months, median of 23 months). No significant differences were shown between the surgery (S) and S + RT groups ( p = 0.146) in the M0 (without metastasis) arm. However, there was a statistically significant difference in OS between the S and S + RT groups in the M1 (with metastasis) arm (median of 44.6 months for the S group and 80.9 months for the S + RT group), p = 0.004. The mean survival was significantly longer for M0 patients than for M1 patients when treated with S only (S arm), that is, 82.1 months versus 44.6 months, respectively (log-rank p = 0.000). We also noted that when patients received adjuvant RT (S + RT arm), there were no significant differences between the M0 and M1 groups (median of 90.6 and 81.0 months, p = 0.704, respectively). Age at diagnosis, chemotherapy, T stage and N stage were significant factors for OS in the M0 arm. Interestingly, radiotherapy was the only significant factor for OS with a multivariate HR for death of 0.502 (95% CI 0.206–0.750, p = 0.006) in the M1 arm. Conclusions: RT may be carefully used in patients who are negative for metastases. Using SEER data, we identified a significant survival advantage with the combination of radiotherapy and surgery in NECC with metastases. This suggests that active local treatment should be conducted and has a significant impact on OS, even if a distant metastasis has occurred.

ULK2 suppresses glycolysis to attenuate cisplatin resistance in ovarian cancer organoid via c-Jun phosphorylation

Objective Resistance to platinum-based chemotherapy remains a key obstacle in ovarian cancer treatment. This study aims to investigate the role of Uncoordinated 51-like kinase 2 (ULK2) in chemoresistance of ovarian cancer and elucidate its underlying mechanisms using 3D patient-derived organoids. Methods Survival analysis was first performed using the Kaplan‒Meier plotter database. Immunohistochemical profiling delineated differential ULK2 expression patterns between chemoresistant and chemosensitive ovarian cancer tissue samples and organoids. ULK2 overexpression was achieved in cisplatin-resistant ovarian cancer organoids via lentiviral vector transduction. Then, we conducted an in-depth examination of the alterations in phosphorylated proteins induced by ULK2 overexpression using phosphoproteomics technology. To investigate the influence of ULK2 on chemosensitivity in ovarian cancer, Cell Counting Kit-8 (CCK-8) and in vivo experiments were conducted. Glycolysis was quantitatively assessed, and the underlying molecular mechanism was systematically investigated. Results ULK2 high-expression ovarian cancer exhibited enhanced chemosensitivity and conferred survival advantage. CCK-8 and mouse experiments demonstrated that ULK2 overexpression decreased cisplatin resistance in patient-derived organoids. Gene Ontology (GO) analysis of phosphoproteomics profiling highlighted the predominant role of ULK2 in metabolic processes with experimental validation demonstrating its suppression of glycolysis. Mechanistically, ULK2 attenuated c-Jun expression by phosphorylation of c-Jun at Ser243. Moreover, c-Jun overexpression counteracted the chemosensitivity and glycolytic suppression induced by the ectopic ULK2 expression in ovarian cancer. Conclusions ULK2 overcomes cisplatin resistance in ovarian cancer by downregulating glycolysis, a process mediated by phosphorylation-induced c-Jun degradation. These findings emphasized the role of ULK2 as a tumor suppressor, offering novel insights for chemotherapy in ovarian cancer.

Publisher

SAGE Publications

ISSN

0036-8504