Identification of a circadian gene signature that predicts overall survival in lung adenocarcinoma

PeerJ

article

Xinliang Gao¹  Mingbo Tang¹  Suyan Tian²  Jialin Li¹  Wei Liu¹ 

[1] Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, Jilin Province;Division of Clinical Research, The First Hospital of Jilin University, Changchun, Jilin Province

关键词: Lung adenocarcinoma;    Circadian clock;    Overall survival;    Gene signature;    TCGA;   

DOI  :  10.7717/peerj.11733

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

BackgroundLung adenocarcinoma (LUAD) is one of the most common subtypes of lung cancer which is the leading cause of death in cancer patients. Circadian clock disruption has been listed as a likely carcinogen. However, whether the expression of circadian genes affects overall survival (OS) in LUAD patients remains unknown. In this article, we identified a circadian gene signature to predict overall survival in LUAD.MethodsRNA sequencing (HTSeq-FPKM) data and clinical characteristics were obtained for a cohort of LUAD patients from The Cancer Genome Atlas (TCGA). A multigene signature based on differentially expressed circadian clock-related genes was generated for the prediction of OS using Least Absolute Shrinkage and Selection Operator (LASSO)-penalized Cox regression analysis, and externally validated using the GSE72094 dataset from the GEO database.ResultsFive differentially expressed genes (DEGs) were identified to be significantly associated with OS using univariate Cox proportional regression analysis (P < 0.05). Patients classified as high risk based on these five DEGs had significantly lower OS than those classified as low risk in both the TGCA cohort and GSE72094 dataset (P 1, P < 0.001). Receiver operating characteristic (ROC) curves confirmed its prognostic value. Gene set enrichment analysis (GSEA) showed that Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to cell proliferation, gene damage repair, proteasomes, and immune and autoimmune diseases were significantly enriched.ConclusionA novel circadian gene signature for OS in LUAD was found to be predictive in both the derivation and validation cohorts. Targeting circadian genes is a potential therapeutic option in LUAD.

【 授权许可】

CC BY