m6A RNA methylation regulators were associated with the malignancy and prognosis of ovarian cancer

N6-methyladenosine (m6A) RNA methylation regulators play a regulatory role in tumor pathogenesis and development. However, the role of m6A regulator genes in ovarian cancer (OC) has not been fully elucidated. This study aims to investigate the mRNA expressions, clinicopathological features, and prognostic values of m6A regulators in OC. Here, we demonstrate that the 17 m6A RNA methylation regulators are differentially expressed in ovarian cancer and normal tissues. By using consensus clustering, all ovarian cancer patients can be divided into two subgroups (cluster 1 and 2) based on the expression of 17 m6A RNA methylation regulators. Using Gene Set Enrichment Analysis, we identified that cluster 1 was most connected to oxidative phosphorylation pathways. Regression models identified that prognosis is associated with HNRNPA2B1, KIAA1429, and WTAP. qRT-PCR result show that the expression trends of HNRNPA2B1 and KIAA1429 are consistent with the predicted results. Multivariate Cox regression analysis results show that the risk score was an independent predictive factor in OV. The overall survival of high-risk patients was significantly shorter than that of low-risk patients. ROC curve analysis showed that the prognostic signature precisely predicted the 5-year survival of OV patients. A nomogram was developed to predict each patient’s survival probability and well calibrated and showed a satisfactory discrimination. Dendritic fraction, macrophage fraction, and neutrophil fraction showed higher fraction in high-risk patients. In conclusion, m6A RNA methylation regulators are vital participants in ovarian cancer pathology, and three-gene mRNA levels are valuable factors for prognosis predictions.

N6-甲基腺嘌呤（N6-methyladenosine，m6A）RNA甲基化调控因子在肿瘤发生与发展中发挥关键调控作用。然而，m6A调控基因在卵巢癌（ovarian cancer，OC）中的作用尚未完全阐明。本研究旨在探究m6A调控因子在卵巢癌中的mRNA表达水平、临床病理特征及预后价值。本研究证实，17种m6A RNA甲基化调控因子在卵巢癌组织与正常组织中存在显著差异表达。通过一致性聚类分析，基于这17种m6A RNA甲基化调控因子的表达谱，可将所有卵巢癌患者划分为两个亚组（聚类1与聚类2）。借助基因集富集分析（Gene Set Enrichment Analysis，GSEA），我们发现聚类1主要与氧化磷酸化通路密切相关。回归模型分析显示，患者预后与HNRNPA2B1、KIAA1429及WTAP这三个基因显著相关。定量实时聚合酶链反应（quantitative real-time polymerase chain reaction，qRT-PCR）结果表明，HNRNPA2B1与KIAA1429的表达趋势与预测结果完全一致。多因素Cox回归分析结果显示，风险评分是卵巢癌（OV）独立的预后预测因子。高危患者的总生存期显著短于低危患者。受试者工作特征曲线（Receiver Operating Characteristic curve，ROC曲线）分析证实，该预后特征可精准预测卵巢癌患者的5年生存率。本研究构建了列线图（nomogram）以预测每位患者的生存概率，该列线图校准良好且展现出优异的区分效能。高危患者的树突状细胞分数、巨噬细胞分数及中性粒细胞分数均显著高于低危患者。综上，m6A RNA甲基化调控因子是卵巢癌病理进程中的关键参与者，且这三种基因的mRNA水平可作为有效的预后预测因子。