Shao Yang, Kong Jing, Xu Hanzi, Wu Xiaoli, Cao YuePeng, Li Weijian, Han Jing, Li Dake, Xie Kaipeng, Wu Jiangping
Nanjing Maternity and Child Health Care Institute, Nanjing Maternity and Child Health Care Hospital, Women's Hospital of Nanjing Medical University, Nanjing, China.
The First People's Hospital of Zhangjiagang City, The Zhangjiagang Affiliated Hospital of Soochow University, Suzhou, China.
Front Cell Dev Biol. 2021 Mar 11;9:570898. doi: 10.3389/fcell.2021.570898. eCollection 2021.
The association of opioid binding protein cell adhesion molecule-like (OPCML) gene methylation with ovarian cancer risk remains unclear. 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. 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 < 0.05). Sensitivity analysis showed that the finding was robust. No publication bias was observed in Begg's ( = 0.458) and Egger's tests ( = 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. Our findings support that OPCML methylation is associated with an increased risk of ovarian cancer.
阿片样物质结合蛋白细胞粘附分子样（OPCML）基因甲基化与卵巢癌风险之间的关联仍不明确。我们通过检索PubMed、Web of Science、ScienceDirect和万方数据库来确定符合条件的研究。采用比值比（OR）和95%置信区间（95%CI）来确定OPCML甲基化与卵巢癌风险之间的关联。采用Meta回归和亚组分析来评估异质性来源。此外，我们分析了基因表达综合数据库（GEO）和癌症基因组图谱（TCGA）数据集以验证我们的发现。我们的研究纳入了来自八项符合条件研究的476例卵巢癌患者和385例对照。在随机效应模型下，癌症组与对照组的合并OR为33.47（95%CI = 12.43 - 90.16）。根据样本类型、对照类型、方法和样本量进行的亚组分析中，该关联仍然显著（均P < 0.05）。敏感性分析表明该发现具有稳健性。在Begg检验（P = 0.458）和Egger检验（P = 0.261）中未观察到发表偏倚。我们进一步发现OPCML甲基化与Ⅲ/Ⅳ期（OR = 4.20，95%CI = 1.59 - 11.14）以及低分化分级（OR = 4.37；95%CI = 1.14 - 16.78）相关。基于GSE146552和GSE155760，我们验证了与正常组织相比，OPCML启动子区域的三个CpG位点（cg16639665、cg23236270、cg15964611）在癌组织中显著更高。然而，基于TCGA卵巢癌数据，我们未观察到OPCML甲基化与临床病理参数及总生存期之间的关联。我们的研究结果支持OPCML甲基化与卵巢癌风险增加相关。
