Endometriosis significantly impacts women’s health and fertility, with cell aging playing a crucial role in its development. This study utilized a multi-omic summary Mendelian randomization (SMR) analysis, integrating genome-wide association studies (GWAS), expression quantitative trait loci (eQTLs), methylation quantitative trait loci (mQTLs), and protein quantitative trait loci (pQTLs). The goal was to identify genes that exhibit causal associations between cell aging and endometriosis. Validation was conducted using the FinnGen R10 and UK Biobank cohorts. The SMR and HEIDI tests evaluated the genetic variants linked to both cell aging and endometriosis risk. Colocalization analysis revealed shared genetic variants, uncovering significant associations between the two conditions. A total of 196 CpG sites in 78 genes, alongside 18 eQTL-associated genes and 7 pQTL-associated proteins, were identified. Notably, the MAP3K5 gene displayed contrasting methylation patterns linked to endometriosis risk. In validation cohorts, the THRB gene and ENG protein were confirmed as risk factors. The findings suggest a causal mechanism where specific methylation patterns downregulate the MAP3K5 gene, heightening endometriosis risk, highlighting it and associated pathways as potential therapeutic targets.

Cervical cancer is identified as one of the most familiar female malignancies. And a number of studies have elucidated that long non-coding RNAs (lncRNAs) participated in the initiation and progress of incalculable tumors, so lncRNAs have attracted more and more attention from researchers. The purpose of the study is to figure out the role and molecular regulation mechanism of DGUOK-AS1 in cervical cancer. The role of DGUOK-AS1 in cervical cancer was validated by CCK-8, colony formation, EdU, flow cytometry and western blot assays. The interactions among DGUOK-AS1, miR-653-5p and EMSY were confirmed by qRT-PCR, western blot, RNA pull down, RIP and luciferase reporter assays. The expression of DGUOK-AS1 is significantly high in cervical cancer cells. Further, shortage of DGUOK-AS1 repressed cell proliferation and stimulated cell apoptosis in cervical cancer. Then miR-653-5p, which low expressed in cervical cancer cells, was found to be sponged by DGUOK-AS1. Similarly, miR-653-5p mimics inhibited cervical cancer proliferation. Moreover, EMSY served as the target gene of miR-653-5p, and DGUOK-AS1 could regulate EMSY expression via sponging miR-653-5p. Besides, EMSY possessed high obviously high expression in cervical cancer cells. Final rescuing assays illustrated that both pcDNA3.1/EMSY and miR-653-5p inhibitor could remedy the suppressive role of DGUOK-AS1 downregulation in cervical cancer cell proliferation. DGUOK-AS1 promotes the proliferation cervical cancer through regulating miR-653-5p/EMSY, which may be helpful to make a deep research about the development of cervical cancer.

Background: The effect of ovarian-sparing surgery versus ovariectomy on prognosis in early cervical adenocarcinoma is controversial. The aim of this study was to compare the effect of ovary preservation versus ovariectomy on the prognosis of patients with cervical adenocarcinoma. Methods: A literature search was conducted of the PubMed, Excerpta Medica Database, Medline, Central, China National Knowledge Infrastructure databases, and China Science Periodical Database. The subjects of the literature study were patients with cervical adenocarcinoma. The literature compared the prognostic impact of ovary-sparing versus ovariectomy surgery. The Newcastle-Ottawa Scale was used to evaluate the quality of the articles. The Chi-square test was used to test the heterogeneity of the articles, and the random-effects model was used if the results indicated heterogeneity. A subgroup analysis and sensitivity analysis were used to examine the source of heterogeneity. If there was no heterogeneity among the articles, a fixed-effects model was used. Publication bias was evaluated using funnel plots and Egger test. Results: A total of 3,467 patients with stage IA–IB cervical adenocarcinoma from 5 articles were included in the meta-analysis, of whom 995 had ovarian preservation and 1,895 had ovariectomy. There was no statistically significant difference in the 5-year overall survival (OS) between the stage IA–IIB cervical adenocarcinoma patients in the ovariectomy group and the ovarian preservation group (P=0.14). Additionally, there was no heterogeneity among these articles, and no publication bias (P>0.05). There was no significant difference in the 5-year progression free survival (PFS) between the stage IA–IIB cervical adenocarcinoma patients in the ovariectomy group and the ovarian preservation group (P=0.11). Additionally, there was no heterogeneity among these articles, and no publication bias (P>0.05). There was no significant difference in the 5-year disease specific survival (DSS) between the stage IA–IIB cervical adenocarcinoma patients in the ovariectomy group and the ovarian preservation group (P=0.48). Additionally, there was no heterogeneity among these articles, and no publication bias (P>0.05). Conclusions: There was no statistically significant difference in 5-year OS, PFS and DSS between ovarian-sparing surgery and oophorectomy for early-stage cervical adenocarcinoma. High-quality randomized controlled trials are still needed to verify this conclusion.

Original Article Screening of prognostic immune genes and establishment of prognostic model of cervical adenocarcinoma based on bioinformatics analysis Yunhua Yi, Jiangxin Sheng, Jichan Nie

Background: Previous studies have suggested that aging may influence reproductive functions of female. Nonetheless, the causal relationship between aging and endometriosis has yet to be completely understood. Objective: This study aims to determine whether aging had a causal association with the incidence of endometriosis. Methods: We conducted bidirectional MR analyses to evaluate the causal relationship between aging biomarkers, particularly leukocyte telomere length (LTL), and endometriosis risk. Instrumental variables for LTL were derived from the UK Biobank GWAS, while endometriosis-associated variants were obtained from the FinnGen GWAS dataset. Subgroup analyses were performed to investigate the association between LTL and endometriosis subtypes. Additionally, validation was performed using independent GWAS meta-analysis datasets. Results: Inverse variance-weighted (IVW) analysis revealed a significant association between longer LTL and an increased risk of endometriosis (OR-IVW = 1.276, 95% CI: 1.143 to 1.424, FDR-adjusted P = 7.00E-5), with consistent findings across multiple MR methods. Sensitivity analysis using an independent GWAS meta-analysis dataset did not confirm the LTL-endometriosis association (OR-IVW = 1.128, 95% CI: 0.140 to 9.115, P = 0.910). Bidirectional MR analysis found no causal relationship between endometriosis and LTL. Subgroup analyses indicated that longer LTL was significantly associated with endometriosis of the ovary (OR-IVW = 1.343, 95% CI: 1.143 to 1.577, P = 3.00E-4) and endometriosis of the rectovaginal septum and vagina (OR-IVW = 1.336, 95% CI: 1.064 to 1.676, P = 0.013), while no significant association was found with endometriosis of the pelvic peritoneum. Conclusion: Our findings suggest that longer LTL may contribute to an increased risk of endometriosis, particularly in ovarian and rectovaginal subtypes. However, no causal effect of endometriosis on aging was observed. The lack of replication in independent datasets highlights the potential influence of population heterogeneity and dataset-specific factors, warranting further validation in diverse cohorts.