Correlation of expression of circadian genes with liver metastasis and outcomes in colorectal cancer.

Abstract

10560 Background: Circadian rhythms are daily oscillations in various biological processes, generated by the feedback loops of eight core circadian genes. These eight genes are Clock, casein kinase I ϵ (CKIϵ), cryptochrome1 (Cry1), cryptochrome2 (Cry2), Period1 (Per1), Period2 (Per2), Period3 (Per3), and Bmal1. Recent studies have suggested that circadian genes participate in the growth and development of various cancers. This study examined the relations of circadian gene expression to clinicopathological factors and outcomes in patients with colorectal cancer. Methods: We studied surgical specimens of cancer tissue and adjacent normal mucosa obtained from 202 patients with untreated colorectal cancer. The relative expression levels of the eight circadian genes in the specimens were measured by quantitative real-time, reverse-transcription polymerase chain reaction. Results: Expressions of the Clock gene and the CKIϵ gene in cancer tissue were significantly higher than those in adjacent normal mucosa (p < 0.0001, p < 0.0001). Expressions of the Per1 gene and the Per3 gene in cancer tissue were significantly lower than those in adjacent normal mucosa (p = 0.043, p = 0.010). Analysis of the relations between clinicopathological features and expressions of the eight circadian genes in cancer tissue showed that high expression of the Bmal1 gene and low expression of the Per1 gene correlated with liver metastasis. On analysis of the relations between outcomes and expressions of the eight circadian genes, high expression of the Per2 gene was associated with significantly better outcomes than low expression of the Per2 gene (p = 0.0038). Conclusions: Our results suggest that overexpression of the Bmal1 gene and reduced expression of the Per1 gene might promote liver metastasis, whereas reduced expression of the Per2 gene might shorten survival in patients with colorectal cancer. Overexpression of the Bmal1 gene and reduced expression of the Per1 gene may thus be useful predictors of liver metastasis. Moreover, reduced expression of the Per2 gene may also be a useful prognostic factor in patients with colorectal cancer. No significant financial relationships to disclose.