m6A RNA 甲基化调控因子的表达及其在肝内胆管癌中的临床预测价值。

Expression of m6A RNA Methylation Regulators and Their Clinical Predictive Value in Intrahepatic Cholangiocarcinoma.

机构信息

Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, 200041 Shanghai, China.

Department of Hepatobiliary Surgery, Changzheng Hospital, Second Military Medical University, 200041 Shanghai, China.

出版信息

Front Biosci (Landmark Ed). 2023 Jun 27;28(6):120. doi: 10.31083/j.fbl2806120.

DOI:10.31083/j.fbl2806120

PMID:37395024

Abstract

BACKGROUND

N6-methyladenosine (m6A) RNA methylation regulators have been implicated in the carcinogenesis and progress of a variety of cancers. Until now, the effects of them on intrahepatic cholangiocarcinoma (ICC) have been poorly understood.

METHODS

We used the GEO databases to systematically evaluate the expression profiles of 36 m6A RNA methylation regulators in ICC patients and produced a signature to assess its prognostic values. experiments were implemented to confirm the expression level.

RESULTS

Compared to normal intrahepatic bile duct tissues, more than half of these 36 genes showed different levels of expression in ICC tissues. Two groups emerged from the consensus cluster analysis of these 36 genes. The two cluster of patients had significantly different clinical outcomes. In addition, we created a m6A-related prognostic signature that performed exceptionally well in the prognostic categorization of ICC patients, based on the ROC curves, Kaplan-Meier curves, and univariate and multivariate Cox regression analyses. Further research showed that there was a significant association between the m6A-related signature and the manifestations of tumor immune microenvironment in ICC. The expression level and biological effect of METTL16, one of the two m6A RNA methylation regulators incorporated in the signature, were confirmed and explored by using experiments.

CONCLUSIONS

This analysis revealed the predictive roles of m6A RNA methylation regulators in ICC.

摘要

背景

N6-甲基腺苷（m6A）RNA 甲基化调节剂参与了多种癌症的发生和进展。到目前为止，它们对肝内胆管癌（ICC）的影响还知之甚少。

方法

我们使用 GEO 数据库系统地评估了 36 种 m6A RNA 甲基化调节剂在 ICC 患者中的表达谱，并构建了一个特征来评估其预后价值。进行了实验来验证表达水平。

结果

与正常的肝内胆管组织相比，这 36 个基因中的一半以上在 ICC 组织中表现出不同程度的表达。对这 36 个基因进行共识聚类分析后，出现了两组。两组患者的临床结局有显著差异。此外，我们根据 ROC 曲线、Kaplan-Meier 曲线以及单因素和多因素 Cox 回归分析，基于这 36 个基因，创建了一个 m6A 相关的预后特征，该特征在 ICC 患者的预后分类中表现出色。进一步的研究表明，m6A 相关特征与 ICC 中肿瘤免疫微环境的表现之间存在显著关联。通过实验验证并探讨了signature 中包含的两个 m6A RNA 甲基化调节剂之一 METTL16 的表达水平和生物学效应。