OPCML Methylation and the Risk of Ovarian Cancer: A Meta and Bioinformatics Analysis

Background: The association of opioid binding protein cell adhesion molecule-like (OPCML) gene methylation with ovarian cancer risk remains unclear. Methods: We identified eligible studies by searching the PubMed, Web of Science, ScienceDirect, and Wanfang databases. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to determine the association of OPCML methylation with ovarian cancer risk. Meta-regression and subgroup analysis were used to assess the sources of heterogeneity. Additionally, we analyzed the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets to validate our findings. Results: Our study included 476 ovarian cancer patients and 385 controls from eight eligible studies. The pooled OR was 33.47 (95% CI = 12.43-90.16) in the cancer group vs. the control group under the random-effects model. The association was still significant in subgroups according to sample type, control type, methods, and sample sizes (all P < 0.05). Sensitivity analysis showed that the finding was robust. No publication bias was observed in Begg's (P = 0.458) and Egger's tests (P = 0.261). We further found that OPCML methylation was related to III/IV (OR = 4.20, 95% CI = 1.59-11.14) and poorly differentiated grade (OR = 4.37; 95% CI = 1.14-16.78). Based on GSE146552 and GSE155760, we validated that three CpG sites (cg16639665, cg23236270, cg15964611) in OPCML promoter region were significantly higher in cancer tissues compared to normal tissues. However, we did not observe the associations of OPCML methylation with clinicopathological parameters and overall survival based on TCGA ovarian cancer data. Conclusion: Our findings support that OPCML methylation is associated with an increased risk of ovarian cancer.