Identification of molecular subtypes in lung adenocarcinoma based on DNA methylation and gene expression profiling-a bioinformatic analysis.

Content Provider	Europe PMC
Author	Wang, Shuying Liang, Xiaoxing Guo, Ruomi Gong, Jiao Zhong, Xiaolong Liu, Yulin Wang, Deqing Hao, Yanmei Hu, Bo
Copyright Year	2022
Abstract	BackgroundMolecular typing based on deoxyribonucleic acid (DNA) methylation and gene expression can extend understandings of the molecular mechanisms involved in lung adenocarcinoma (LUAD) and enhance current diagnostic, treatment, and prognosis prediction approaches.MethodsGene expression and DNA methylation data sets of LUAD were obtained from The Cancer Genome Atlas (TCGA), and the differential gene and methylation expression levels were analyzed.ResultsWe successfully divided the LUAD samples into 2 clinically relevant subtypes with significantly different survival times and tumor stages according to the transcriptome and methylation data. We found significant differences in the survival status, age, gender, tumor stage, node stage, and clinical stage between the 2 subtypes. The hub genes identified in the subnetworks, including NCAPG, CCNB1, DLGAP5, HLA-DQA1, HLA-DPA1, HLA-DPB1, SFTP, SCGBA1A, and SFTPD, were correlated with the cell cycle and immune system. The Gene Ontology annotation of the hub genes showed that the biological processes included organelle fission mitotic nuclear division, and sister chromatid segregation. The cellular components included chromosomal region, spindle, and kinetochore. The molecular functions included tubulin-binding, microtubule-binding, and DNA replication origin binding. The Kyoto Encyclopedia of Genes and Genomes signaling pathways related to the hub genes mainly included the cell cycle, human T-cell leukemia virus (type 1) infection, inflammatory bowel disease, and the intestinal immune network for immunoglobulin A production. The clinical stage difference was also confirmed in the validation group using the GSE32863 data set.ConclusionsOur findings extend understandings of the pathogenesis of LUAD and can be used to improve current diagnosis, treatment, and prognosis prediction strategies.
ISSN	23055839
Volume Number	10
PubMed Central reference number	PMC9469139
Issue Number	16
PubMed reference number	36111050
Journal	Annals of Translational Medicine [Ann Transl Med]
e-ISSN	23055847
DOI	10.21037/atm-22-3340
Language	English
Publisher	AME Publishing Company
Publisher Date	2022-08-01
Access Restriction	Open
Rights License	Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0. 2022 Annals of Translational Medicine. All rights reserved.
Subject Keyword	Lung adenocarcinoma (LUAD) cancer subtypes The Cancer Genome Atlas (TCGA) Gene Expression Omnibus (GEO) methylation
Content Type	Text
Resource Type	Article
Subject	Medicine