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

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单位: [1]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Thorac Surg, 1095 Jiefang Ave, Wuhan 430030, Hubei, Peoples R China [2]YuceBio Technol Co Ltd, Dabaihui Ctr, 4th Floor,Phase 1,2002 Shenyan Rd,Haishan St, Shenzhen 518000, Guangdong, Peoples R China [3]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Oncol, 1095 Jiefang Ave, Wuhan 430030, Hubei, Peoples R China
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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.

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大类 | 4 区 医学
小类 | 4 区 生物工程与应用微生物 4 区 遗传学 4 区 医学:研究与实验 4 区 病理学
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Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Q2 PATHOLOGY Q2 GENETICS & HEREDITY Q3 MEDICINE, RESEARCH & EXPERIMENTAL
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第一作者单位: [1]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Thorac Surg, 1095 Jiefang Ave, Wuhan 430030, Hubei, Peoples R China
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