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

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.

Firefighting, per‐ and polyfluoroalkyl substances, and DNA methylation of genes associated with prostate cancer risk

“…Depending on the transcript variant, this region spans either the transcription start site or the first exon of the gene (Nassar et al, 2023) and may have an impact on downstream transcription. FAM83A is a lncRNA whose expression is positively associated with breast cancer, lung adenocarcinoma, and colorectal cancer (Cao et al, 2022; Jin et al, 2022; Liu et al, 2021; Yu et al, 2020). Although no evidence exists which explicitly ties expression of FAM83A to prostate cancer risk or prognosis, we selected this region for analysis since DNA methylation in 8q24 was previously linked to prostate cancer risk (Barry et al, 2017).…”

Definition of a Novel Cuproptosis-Relevant lncRNA Signature for Uncovering Distinct Survival, Genomic Alterations, and Treatment Implications in Lung Adenocarcinoma

“…Necroptosis and ferroptosis are newly discovered programmed cell deaths recently [ 47 ]. AL161431.1 acts as an autophagy- and prognosis-relevant lncRNA in NSCLC [ 48 ], with epigenetically aberrant regulation in LUAD [ 49 ] and pancreatic adenocarcinoma [ 50 ]. In addition, AL161431.1 is linked to hypoxia status and immune microenvironment of LUAD [ 51 ].…”

Association between rheumatoid arthritis and serum vitamin C levels in Adults: Based on the National health and Nutrition Examination survey database

“…Studies have reported that chronic lower respiratory illness mortality is enhanced by low blood vitamin C levels( Salo et al, 2022 ). A cross-sectional study manifested that serum vitamin C levels are significantly associated with fibrosis in male and overweight or obese non-alcoholic fatty liver disease patients( Cao et al, 2022 ). However, association between serum vitamin C levels and the risk of rheumatoid arthritis has not been fully studied.…”