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基于生物信息学分析鉴定的子宫内膜癌 8-m6A RNA 甲基化调控预后特征。

Identification of an eight-m6A RNA methylation regulator prognostic signature of uterine corpus endometrial carcinoma based on bioinformatics analysis.

机构信息

Department of TCM Gynecology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China.

Department of Anorectal Surgery, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China.

出版信息

Medicine (Baltimore). 2021 Dec 10;100(49):e27689. doi: 10.1097/MD.0000000000027689.

Abstract

N6-methyladenosine (m6A) methylation is proved to play a significant role in human cancers. This study aimed to explore the association between m6A ribonucleic acid (RNA) methylation regulators and uterine corpus endometrial carcinoma (UCEC), and build a prognostic signature of m6A regulators for UCEC.RNA-seq transcriptome data and clinicopathological data of UCEC were downloaded from the Cancer Genome Atlas database. We compared the expression of 23 m6A-regulators in tumor tissues and nontumor tissues. Then we classified the data into 3 clusters by consensus clustering analysis. Several regulators were picked out as the prognostic signature of patients with UCEC based on least absolute shrinkage and selection operator Cox regression analysis. Additionally, we established a predictive nomogram to calculate survival times. Finally, we used receiver operating characteristic curve, univariate Cox regression analysis, and multivariate Cox regression analysis to further verify the prognostic value of the risk signature consisting of m6A regulators.The expression of 18/23 m6A regulators was significantly different in UCEC compared with normal samples. Gene ontology functional analysis of these regulators revealed that they were mainly participated in RNA splicing, stabilization, modification, and degradation. LRPPRC, IGFBP2, KIAA1429, IGFBP3, FMR1, YTHDF1, METTL14, and YTHDF2 were selected to construct the risk signature and predictive nomogram. The results of receiver operating characteristic curve, univariate Cox regression analysis, and multivariate Cox regression analysis for the risk signature showed a good predictive performance for UCEC.The risk signature of 8-m6A regulators has potential prognostic value for patients with UCEC.

摘要

N6-甲基腺苷(m6A)甲基化被证明在人类癌症中发挥重要作用。本研究旨在探讨 m6A 核糖核酸(RNA)甲基化调节剂与子宫体子宫内膜癌(UCEC)之间的关联,并为 UCEC 构建 m6A 调节剂的预后特征。从癌症基因组图谱数据库下载 UCEC 的 RNA-seq 转录组数据和临床病理数据。我们比较了肿瘤组织和非肿瘤组织中 23 种 m6A 调节剂的表达。然后,我们通过共识聚类分析将数据分为 3 个簇。基于最小绝对值收缩和选择算子 Cox 回归分析,选择了几种调节剂作为 UCEC 患者的预后特征。此外,我们建立了一个预测列线图来计算生存时间。最后,我们使用接受者操作特征曲线、单因素 Cox 回归分析和多因素 Cox 回归分析进一步验证由 m6A 调节剂组成的风险特征的预后价值。与正常样本相比,18/23 种 m6A 调节剂在 UCEC 中的表达明显不同。这些调节剂的基因本体功能分析表明,它们主要参与 RNA 剪接、稳定、修饰和降解。LRPPRC、IGFBP2、KIAA1429、IGFBP3、FMR1、YTHDF1、METTL14 和 YTHDF2 被选择来构建风险特征和预测列线图。风险特征的接收器操作特征曲线、单因素 Cox 回归分析和多因素 Cox 回归分析结果表明,该风险特征对 UCEC 具有良好的预测性能。由 8 种 m6A 调节剂组成的风险特征对 UCEC 患者具有潜在的预后价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec53/8663882/a54866d25489/medi-100-e27689-g001.jpg

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