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5-甲基胞嘧啶相关长链非编码RNA作为结肠腺癌潜在的预后生物标志物

5mC-Related lncRNAs as Potential Prognostic Biomarkers in Colon Adenocarcinoma.

作者信息

Huang Yinghui, Huang Huiqian, Wang Yong, Liu Hui, Huang Yingdan

机构信息

Key Laboratory of Adolescent Cyberpsychology and Behavior, Ministry of Education, Wuhan 430056, China.

School of Psychology, Central China Normal University, Wuhan 430056, China.

出版信息

Biology (Basel). 2022 Feb 1;11(2):231. doi: 10.3390/biology11020231.

DOI:10.3390/biology11020231
PMID:35205097
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8868594/
Abstract

Globally, colon adenocarcinoma (COAD) is one of the most frequent types of malignant tumors. About 40~50% of patients with advanced colon adenocarcinoma die from recurrence and metastasis. Long non-coding RNAs (lncRNAs) and 5-methylcytosine (5mC) regulatory genes have been demonstrated to involve in the progression and prognosis of COAD. The goal of this study was to explore the biological characteristics and potential predictive value of 5mC-related lncRNA signature in COAD. In this research, The Cancer Genome Atlas (TCGA) was utilized to obtain the expression of genes and somatic mutations in COAD, and Pearson correlation analysis was used to select lncRNAs involved in 5mC-regulated genes. Furthermore, we applied univariate Cox regression and Lasso Cox regression to construct 5mC-related lncRNA signature. Then Kaplan-Meier survival analysis, principal components analysis (PCA), receiver operating characteristic (ROC) curve, and a nomogram were performed to estimate the prognostic effect of the risk signature. GSEA was utilized to predict downstream access of the risk signature. Finally, the immune characteristics and immunotherapeutic signatures targeting this risk signature were analyzed. In the results, we obtained 1652 5mC-related lncRNAs by Pearson correlation analysis in the TCGA database. Next, we selected a risk signature that comprised 4 5mC-related lncRNAs by univariate and Lasso Cox regression. The prognostic value of the risk signature was proven. Finally, the biological mechanism and potential immunotherapeutic response of the risk signature were identified. Collectively, we constructed the 5mC-related lncRNA risk signature, which could provide a novel prognostic prediction of COAD patients.

摘要

在全球范围内,结肠腺癌(COAD)是最常见的恶性肿瘤类型之一。约40%至50%的晚期结肠腺癌患者死于复发和转移。长链非编码RNA(lncRNAs)和5-甲基胞嘧啶(5mC)调控基因已被证明与COAD的进展和预后有关。本研究的目的是探讨5mC相关lncRNA特征在COAD中的生物学特性和潜在预测价值。在本研究中,利用癌症基因组图谱(TCGA)获取COAD中基因的表达和体细胞突变,并采用Pearson相关性分析来选择参与5mC调控基因的lncRNAs。此外,我们应用单变量Cox回归和Lasso Cox回归构建5mC相关lncRNA特征。然后进行Kaplan-Meier生存分析、主成分分析(PCA)、受试者工作特征(ROC)曲线和列线图,以评估风险特征的预后效果。利用基因集富集分析(GSEA)预测风险特征的下游通路。最后,分析了针对该风险特征的免疫特征和免疫治疗特征。结果显示,我们通过对TCGA数据库进行Pearson相关性分析获得了1652个5mC相关lncRNAs。接下来,我们通过单变量和Lasso Cox回归选择了一个由4个5mC相关lncRNAs组成的风险特征。该风险特征的预后价值得到了证实。最后,确定了该风险特征的生物学机制和潜在的免疫治疗反应。总的来说,我们构建了5mC相关lncRNA风险特征,可为COAD患者提供一种新的预后预测方法。

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TET2 mutations are associated with hypermethylation at key regulatory enhancers in normal and malignant hematopoiesis.
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