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Identification of a circadian gene signature that predicts overall survival in lung adenocarcinoma
- Source :
- PeerJ, Vol 9, p e11733 (2021), PeerJ
- Publication Year :
- 2021
- Publisher :
- PeerJ, 2021.
-
Abstract
- Background Lung 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. Methods RNA 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. Results Five 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 < 0.001). Multivariate Cox regression analysis revealed that the five-gene-signature based risk score was an independent predictor of OS (hazard ratio > 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. Conclusion A 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.
- Subjects :
- Lung adenocarcinoma
0301 basic medicine
Bioinformatics
Circadian clock
Biology
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
0302 clinical medicine
Gene signature
medicine
Overall survival
Circadian rhythm
KEGG
Lung cancer
Respiratory Medicine
Gene
General Neuroscience
Cancer
General Medicine
TCGA
medicine.disease
030104 developmental biology
Oncology
030220 oncology & carcinogenesis
Cancer research
Medicine
Adenocarcinoma
General Agricultural and Biological Sciences
Medical Genetics
Subjects
Details
- ISSN :
- 21678359
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- PeerJ
- Accession number :
- edsair.doi.dedup.....20593656513824cb1bc33f42fcc7bcea