Identification and meta-analysis of copy number variation-driven circadian clock genes for colorectal cancer

Abstract

Both copy number variation (CNV) and circadian clock genes play a critical role in the etiology and pathogenesis of colorectal cancer (CRC); however, a comprehensive analysis of CNV-driven circadian clock genes is urgently required. The present study aimed to investigate the systematic associations between somatic cell CNVs and circadian clock gene expression in patients with CRC. Using somatic CNV, legacy clinical information and gene expression data from The Cancer Genome Atlas, 295 genes that were significantly differentially expressed and with significantly different CNV were obtained, and the expression of the genes, among which 15 were circadian clock genes, was significantly associated with CNV. Further analysis revealed that aryl hydrocarbon receptor nuclear translocator-like 2 (ARNTL2) expression and CNV in these circadian clock genes were significantly associated with survival time in patients with CRC, and the expression of ARNTL2 was also significantly associated with the pathological stage of CRC. Gene set enrichment analysis found that ARNTL2 is enriched for gene sets associated with CRC pathogenesis such as the p53 signaling pathway. These results suggest that ARNTL2 may be a promising prognostic biomarker for patients with CRC, and that circadian clock genes play an important role in CRC through CNV.