Department of Obstetrics and Gynecology, 117977The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Internal Medicine, 117977The Affiliated Tumor Hospital of Zhengzhou University, Zhengzhou, China.
Cancer Control. 2020 Jan-Dec;27(1):1073274820960460. doi: 10.1177/1073274820960460.
N6-methyladenosine (m6A) is the most common form of mRNA modification under the field of "RNA epigenetics." However, its role in ovarian cancer (OC) development is poorly understood. In the current study, we aimed to identify gene signatures and prognostic values of m6A RNA methylation regulators.
Specifically, we downloaded Mutations and Copy number variant (CNV) data from the TCGA database for 579 OC patients, then analyzed gene expression and prognosis value using integrative bioinformatics. Thereafter, we verified the related biological processes of Wilms' tumor 1-associating protein (WTAP) gene using Gene set enrichment analysis (GSEA).
Results showed that almost all ovarian cancer patients (99.31%) have CNVs with at least 1 m6A regulatory gene, whereas 83.76% of cases exhibited concurrence of CNVs in more than 4 m6A regulatory genes. Additionally, alteration of m6A regulators was associated with historical grade, whereas integrative bioinformatics and Cox multivariate model analysis revealed a significant correlation between high WTAP expression and worse ovarian cancer outcomes. Moreover, GSEA revealed that high WTAP expression was associated with cell cycle regulation and MYC targets.
Overall, our findings demonstrate the significance of high-frequency genetic alterations of m6A RNA methylation regulators and WTAP's poor prognosis value in OC. These findings provide valuable insights into the role of m6A methylation in OC, and will be vital in guiding development of novel treatment therapies.
N6-甲基腺苷(m6A)是“RNA 表观遗传学”领域中最常见的 mRNA 修饰形式。然而,其在卵巢癌(OC)发展中的作用尚不清楚。在本研究中,我们旨在确定 m6A RNA 甲基化调节剂的基因特征和预后价值。
具体来说,我们从 TCGA 数据库下载了 579 名 OC 患者的突变和拷贝数变异(CNV)数据,然后使用整合生物信息学方法分析基因表达和预后值。之后,我们使用基因集富集分析(GSEA)验证了Wilms 肿瘤 1 相关蛋白(WTAP)基因的相关生物学过程。
结果表明,几乎所有卵巢癌患者(99.31%)的 CNVs 都至少有 1 个 m6A 调节基因,而 83.76%的病例表现出超过 4 个 m6A 调节基因的 CNVs 同时发生。此外,m6A 调节剂的改变与历史分级有关,而整合生物信息学和 Cox 多变量模型分析表明,WTAP 高表达与卵巢癌结局较差显著相关。此外,GSEA 表明,WTAP 高表达与细胞周期调控和 MYC 靶标有关。
总体而言,我们的研究结果表明,m6A RNA 甲基化调节剂的高频遗传改变和 WTAP 预后不良在 OC 中具有重要意义。这些发现为 m6A 甲基化在 OC 中的作用提供了有价值的见解,并将对指导新型治疗方法的发展具有重要意义。