Disturbance of Circadian Gene Expression in Endometrial Cancer: Detection by Real-time Quantitative RT-PCR

Circadian genes control the daily changes of the circadian rhythms in a variety of physiological processes, which in turn regulate many functions in the human body. Disruption of circadian rhythms can have a profound influence on our well-being. We established a set of PCR primers and fluorescent probes to analyze the mRNA levels of nine different circadian genes, and used immunohistochemical methods to study four important circadian proteins in 35 endometrial cancers and their paired non-cancerous tissues. Of these, 13 cases showed reduced expression in all nine circadian genes in the cancerous tissues relative to the paired non-cancerous tissues; the remaining cases showed similar reduced expression in 4-8 of the genes analyzed. Conversely, 3 non-cancerous tissues showed reduced expression in all nine circadian genes in comparison with their respective adjacent cancerous tissues, whereas 6 other non-cancerous tissues showed reduced expression in 6-8 of the circadian genes. These results were also confirmed by immunohistochemical study. Expression of the circadian genes is perturbed in endometrial cancer. Based on these results, we suggest that different circadian rhythms occur in endometrial cancer and non-cancerous tissues. Our results may provide the molecular basis for chronotherapy of endometrial cancer.