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一种由三种mRNA甲基化调节因子组成的新定义风险特征可预测卵巢癌的预后。

A newly defined risk signature, consisting of three mA RNA methylation regulators, predicts the prognosis of ovarian cancer.

作者信息

Fan Lili, Lin Ying, Lei Han, Shu Guang, He Liuer, Yan Zhipeng, Rihan Hai, Yin Gang

机构信息

Department of Pathology, Xiangya Hospital, School of Basic Medical Sciences, Central South University, Changsha, Hunan Province, China.

Department of Immunology, School of Basic Medical Sciences, Central South University, Changsha, Hunan Province, China.

出版信息

Aging (Albany NY). 2020 Sep 20;12(18):18453-18475. doi: 10.18632/aging.103811.

Abstract

N6-methyladenosine (mA) RNA methylation, involved in cancer initiation and progression, is dynamically regulated by the mA RNA methylation regulators. However, the expression of mA RNA methylation regulators in ovarian cancer and their correlation with prognosis remain elusive. Here, we demonstrated that the 18 central mA RNA methylation regulators were expressed differently between ovarian cancer (OC) and normal tissues. By applying consensus clustering, all ovarian cancer patient cases can be divided into three subgroups (cluster1/2/3) based on overall expression levels of all 18 mA RNA methylation regulators. We systematically analyzed the prognostic value of transcription levels of 18 mA RNA methylation regulators in ovarian cancer and found that insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1), vir like mA methyltransferase associated (VIRMA), and zinc finger CCCH-type containing 13 (ZC3H13) yield the highest scores for predicting the prognosis of ovarian cancer. Accordingly, we derived a risk signature consisting of transcription levels of these three selected mA RNA methylation regulators as an independent prognostic marker for OC and validated our findings with data derived from a different ovarian cancer cohort. Moreover, by the Gene Set Enrichment Analysis (GSEA), we demonstrated that the three selected regulators were all correlated with pathways in cancer and WNT signaling pathways. In conclusion, mA RNA methylation regulators are vital participants in ovarian cancer pathology; and IGF2BP1, VIRMA, and ZC3H13 mRNA levels are valuable factors for prognosis prediction and treatment strategy development.

摘要

N6-甲基腺苷(m⁶A)RNA甲基化参与癌症的发生和发展,受m⁶A RNA甲基化调节因子的动态调控。然而,m⁶A RNA甲基化调节因子在卵巢癌中的表达及其与预后的相关性仍不清楚。在此,我们证明18个核心m⁶A RNA甲基化调节因子在卵巢癌(OC)组织和正常组织中的表达存在差异。通过一致性聚类,根据所有18个m⁶A RNA甲基化调节因子的总体表达水平,可将所有卵巢癌患者病例分为三个亚组(cluster1/2/3)。我们系统分析了18个m⁶A RNA甲基化调节因子的转录水平在卵巢癌中的预后价值,发现胰岛素样生长因子2 mRNA结合蛋白1(IGF2BP1)、病毒样m⁶A甲基转移酶相关蛋白(VIRMA)和含锌指CCCH型结构域13(ZC3H13)在预测卵巢癌预后方面得分最高。因此,我们得出了一个风险特征,由这三个选定的m⁶A RNA甲基化调节因子的转录水平组成,作为OC的独立预后标志物,并使用来自不同卵巢癌队列的数据验证了我们的发现。此外,通过基因集富集分析(GSEA),我们证明这三个选定的调节因子均与癌症通路和WNT信号通路相关。总之,m⁶A RNA甲基化调节因子是卵巢癌病理过程中的重要参与者;IGF2BP1、VIRMA和ZC3H13的mRNA水平是预后预测和治疗策略制定的重要因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ae3/7585096/e3dde8200d1e/aging-12-103811-g001.jpg

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