Multi-omics analysis of genomics, epigenomics and transcriptomics for molecular subtypes and core genes for lung adenocarcinoma

BMC Cancer

Yue Zhao¹  Jiwu Zhou¹  Yakun Gao²  He Wang³  Xiaodong Xu⁴ 

[1] Department II of Radiotherapy, Cangzhou Central Hospital, No.16 Xinhua West Road, 061110, Cangzhou, Hebei, China;Department of Ultrasound, Cangzhou Central Hospital, 061110, Cangzhou, Hebei, China;Office of Educational Administration, Hebei Medical University, No.361 Zhongshan East Road, 050017, Shijiazhuang, Hebei, China;School of Clinical Medicine, Cangzhou Medical College, 061001, Cangzhou, Hebei, China;

关键词: Lung adenocarcinoma;    Multi-omics;    Prognosis;    Methylation;    Copy number variation;    Subtype;   

DOI  :  10.1186/s12885-021-07888-4

来源: Springer

【 摘 要 】

BackgroundLung adenocarcinoma (LUAD) is the most frequently diagnosed histological subtype of lung cancer. Our purpose was to explore molecular subtypes and core genes for LUAD using multi-omics analysis.MethodsMethylation, transcriptome, copy number variation (CNV), mutations and clinical feature information concerning LUAD were retrieved from The Cancer Genome Atlas Database (TCGA). Molecular subtypes were conducted via the “iClusterPlus” package in R, followed by Kaplan-Meier survival analysis. Correlation between iCluster subtypes and immune cells was analyzed. Core genes were screened out by integration of methylation, CNV and gene expression, which were externally validated by independent datasets.ResultsTwo iCluster subtypes were conducted for LUAD. Patients in imprinting centre 1 (iC1) subtype had a poorer prognosis than those in iC2 subtype. Furthermore, iC2 subtype had a higher level of B cell infiltration than iC1 subtype. Two core genes including CNTN4 and RFTN1 were screened out, both of which had higher expression levels in iC2 subtype than iC1 subtype. There were distinct differences in CNV and methylation of them between two subtypes. After validation, low expression of CNTN4 and RFTN1 predicted poorer clinical outcomes for LUAD patients.ConclusionOur findings comprehensively analyzed genomics, epigenomics, and transcriptomics of LUAD, offering novel underlying molecular mechanisms for LUAD. Two multi-omics-based core genes (CNTN4 and RFTN1) could become potential therapeutic targets for LUAD.

【 授权许可】

CC BY