Clinicopathological significance of circadian rhythm-related gene expression levels in patients with epithelial ovarian cancer

Acta Obstetricia Et Gynecologica Scandinavica
Hideki TokunagaNobuo Yaegashi

Abstract

Recent studies implicate circadian genes in the regulation of cell cycle, apoptosis, and cell proliferation at a molecular level. These genesey affect cancer incidence, prognosis, and chemosensitivity. In this study, we measured the expression levels of clock genes and correlated their expression levels with clinicopathological parameters in epithelial ovarian cancer. The expression levels of core clock genes, per1, per2, per3, cry1, cry2, Bmal1, clock, and CKIepsilon were quantified by real-time quantitative Reverse transcription-polymerase chain reaction in 83 ovarian cancer tissues and 11 normal ovarian tissues. The expression levels of per1, per2, cry2, clock, CKIepsilon in ovarian cancers were significantly lower than those in normal ovaries. In contrast, cry1 expression was highest among the eight examined clock genes, followed by per3 and Bmal1. Cry1 expression was much higher in cancer than that in normal ovaries. Localized circadian gene expression was determined in cancer cells by in situ hybridization analysis. Cry1 expression was significantly reduced in mucinous and grade 3 tumors. Bmal1 expression was also significantly reduced in mucinous adenocarcinomas as compared to other histologies. In a multivariate analysi...Continue Reading

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