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m6A 相关 lncRNA 特征分析预测结肠癌患者预后和免疫应答。

Characterization of the m6A-related lncRNA signature in predicting prognosis and immune response in patients with colon cancer.

机构信息

Department of Gastroenterology, Panjin Central Hospital Affiliated to Jinzhou Medical University, Panjin 124013, China.

出版信息

J BUON. 2021 Sep-Oct;26(5):1931-1941.

PMID:34761602
Abstract

PURPOSE

Colon adenocarcinoma (COAD) is globally one of the most frequently occurring malignant tumors. The patients' 5-year survival rate with colon cancer was poor. There is a usual form of mRNA modification called N6-methyl adenosine (m6A). It is adjusted by the m6A RNA methylation modulator. Nevertheless, few studies of COAD can fully discuss m6A-related lncRNAs' prognostic function.

METHODS

From The Cancer Genome Atlas (TCGA) database, this study of COAD samples discussed 23 m6A regulator-related lncRNAs systemically. 2 m6A patterns with various clinical results were recognized, and a remarkable correlation between various m6A clusters and tumor immune microenvironment was discovered.

RESULTS

According to prognostic analysis, cluster1 had a higher immune checkpoint programmed death-ligand 1 (PD-L1) expression and a better prognosis. A 6 m6A-related lncRNAs model was constructed through least absolute shrinkage and selection operator (LASSO), univariate, multivariate Cox regression and stratified analysis. The outcomes reported that compared with the low-risk group, high-risk groups that were based on model closely were related to poor overall survival (OS). The study ensured a risk model consisting of 6 m6A-related lncRNAs as independent prognosis predictors. For the expression differences between the two groups, Genomes Pathway Analysis, Kyoto Encyclopedia of Genes (KEGG) and Gene Ontology (GO) biological process analyses were conducted. In addition, on the basis of full analysis of OS, a nomogram based on gender, age, lncRNA feature and the stage was constructed. One year, two years, and three years are the periods when the calibration chart performed best.

CONCLUSIONS

The outcomes of the study confirmed the underlying function of m6A-related lncRNAs and offered fresh perspectives to COAD prognosis.

摘要

目的

结肠腺癌(COAD)是全球最常见的恶性肿瘤之一。结肠癌患者的 5 年生存率较差。有一种常见的 mRNA 修饰形式,称为 N6-甲基腺苷(m6A)。它由 m6A RNA 甲基化调节剂调节。然而,关于 COAD 的研究很少能充分讨论 m6A 相关 lncRNA 的预后功能。

方法

从癌症基因组图谱(TCGA)数据库中,本研究系统地讨论了 COAD 样本中的 23 个 m6A 调节相关 lncRNA。识别出 2 种具有不同临床结果的 m6A 模式,并发现各种 m6A 簇与肿瘤免疫微环境之间存在显著相关性。

结果

根据预后分析,cluster1 具有更高的免疫检查点程序性死亡配体 1(PD-L1)表达和更好的预后。通过最小绝对收缩和选择算子(LASSO)、单因素、多因素 Cox 回归和分层分析构建了一个 6 个 m6A 相关 lncRNAs 模型。结果表明,与低风险组相比,基于模型的高风险组与较差的总生存率(OS)密切相关。该研究确保了一个由 6 个 m6A 相关 lncRNAs 组成的风险模型作为独立的预后预测因子。对于两组之间的表达差异,进行了基因组途径分析、京都基因与基因组百科全书(KEGG)和基因本体论(GO)生物过程分析。此外,在充分分析 OS 的基础上,构建了一个基于性别、年龄、lncRNA 特征和分期的列线图。校准图在一年、两年和三年时表现最佳。

结论

本研究的结果证实了 m6A 相关 lncRNAs 的潜在功能,并为 COAD 的预后提供了新的视角。

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