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通过综合表观遗传分析鉴定和验证 7 个长链非编码 RNA 标志物在表观遗传疾病中的应用。

Identification and Validation of 7-lncRNA Signature of Epigenetic Disorders by Comprehensive Epigenetic Analysis.

机构信息

Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Qiaokou District, Wuhan City, Hubei Province, China 430030.

YuceBio Technology Co., Ltd., 4th Floor, Phase I, Dabaihui Center, No. 2002, Shenyan Road, Haishan Street, Yantian District, Shenzhen City, Guangdong Province, China 518000.

出版信息

Dis Markers. 2022 Feb 21;2022:5118444. doi: 10.1155/2022/5118444. eCollection 2022.

DOI:10.1155/2022/5118444
PMID:35237359
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8885251/
Abstract

The survival rate of patients with lung adenocarcinoma (LUAD) is low. This study analyzed the correlation between the expression of long noncoding RNA (lncRNA) and epigenetic alterations along with the investigation of the prognostic value of these outcomes for LUAD. Differentially expressed lncRNAs were identified based on multiomic data and positively related genes using DESeq2 in R, differentially histone-modifying genes specific to LUAD based on histone modification data, gene enhancers from information collected from the FANTOM5 (Function Annotation Of The Mammalian Genome-5) (fantom.gsc.riken.jp/5) human enhancer database, gene promoters using the ChIPseeker and the human lincRNAs Transcripts database in R, and differentially methylated regions (DMRs) using Bumphunter in R. Overall survival was estimated by Kaplan-Meier, comparisons were performed among groups using log-rank tests to derive differences between sample subclasses, and epigenetic lncRNAs (epi-lncRNAs) potentially relevant to LUAD prognosis were identified. A total of seven dysregulated epi-lncRNAs in LUAD were identified by comparing histone modifications and alterations in histone methylation regions on lncRNA promoter and enhancer elements, including H3K4me2, H3K27me3, H3K4me1, H3K9me3, H4K20me1, H3K9ac, H3K79me2, H3K27ac, H3K4me3, and H3K36me3. Furthermore, 69 LUAD-specific dysregulated epi-lncRNAs were identified. Moreover, lncRNAs-based prognostic analysis of LUAD samples was performed and explored that seven of these lncRNAs, including A2M-AS1, AL161431.1, DDX11-AS1, FAM83A-AS1, MHENCR, MNX1-AS1, and NKILA (7-EpiLncRNA), showed the potential to serve as markers for LUAD prognosis. Additionally, patients having a high 7-EpiLncRNA score showed a generally more unfavorable prognosis compared with those which scored lower. Seven lncRNAs were identified as markers of prognosis in patients with LUAD. The outcomes of this research will help us understand epigenetically aberrant regulation of lncRNA expression in LUAD in a better way and have implications for research advances in the regulatory role of lncRNAs in LUAD.

摘要

肺腺癌 (LUAD) 患者的存活率较低。本研究分析了长链非编码 RNA (lncRNA) 的表达与表观遗传改变之间的相关性，并探讨了这些结果对 LUAD 的预后价值。基于多组学数据和使用 R 中的 DESeq2 识别差异表达的 lncRNA，基于组蛋白修饰数据识别 LUAD 特异性差异组蛋白修饰基因，从 FANTOM5（Function Annotation Of The Mammalian Genome-5）（fantom.gsc.riken.jp/5）人类增强子数据库中收集的基因增强子信息，使用 ChIPseeker 和 R 中的人类 lincRNAs Transcripts 数据库来识别基因启动子，使用 R 中的 Bumphunter 识别差异甲基化区域 (DMR)。通过 Kaplan-Meier 估计总生存率，使用对数秩检验在组间进行比较，以得出样本子类之间的差异，并确定与 LUAD 预后相关的表观遗传 lncRNA (epi-lncRNA)。通过比较组蛋白修饰和 lncRNA 启动子和增强子元件上组蛋白甲基化区域的改变，在 LUAD 中鉴定了七种失调的 epi-lncRNA，包括 H3K4me2、H3K27me3、H3K4me1、H3K9me3、H4K20me1、H3K9ac、H3K79me2、H3K27ac、H3K4me3 和 H3K36me3。此外，还鉴定了 69 种 LUAD 特异性失调的 epi-lncRNA。此外，对 LUAD 样本进行了基于 lncRNA 的预后分析，并探讨了其中七种 lncRNA，包括 A2M-AS1、AL161431.1、DDX11-AS1、FAM83A-AS1、MHENCR、MNX1-AS1 和 NKILA (7-EpiLncRNA)，具有作为 LUAD 预后标志物的潜力。此外，具有高 7-EpiLncRNA 评分的患者的总体预后通常比评分较低的患者更不利。七种 lncRNA 被鉴定为 LUAD 患者预后的标志物。本研究的结果将帮助我们更好地了解 LUAD 中 lncRNA 表达的表观遗传失调调控，并对 lncRNA 在 LUAD 中的调控作用的研究进展具有启示意义。

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