The expression of clock genes cry1 and cry2 in human colorectal cancer and tumor adjacent tissues correlates differently dependent on tumor location

Abstract

Colorectal cancer (CRC) exhibits differences in its features depending on the location of the tumor. The role of the circadian system in carcinogenesis is accepted, and many studies report different clock gene expression in tumors compared to healthy tissue. However, little attention is given to the changes in clock genes in tumors arising from various locations across the colon and rectum. The aim of our study was to investigate the expression of the clock genes cry1 and cry2 in human CRC tissue and tissue adjacent to colorectal tumors in a cohort of 64 patients by real time PCR. Expression of cry1 in the entire patient cohort was higher in tumors compared to adjacent tissues in the right-sided colon but not in the left-sided colorectum. Difference in cry1 expression between tumor and adjacent tissue in the right-sided colon was preserved in women and a trend was observed in men. Higher expression of cry1 in the right-sided colon tumor tissue was associated with worse survival in women and the expression of cry1 in the left-sided colorectum was significantly higher in the adjacent tissue compared to tumor in men but not in women. Expression of cry2 was lower in the tumor than in adjacent tissue in both the right and left-sided colorectum. This trend was generally preserved, but the difference reached significance level only in the male left-sided colon, and cry2 expression in the tumor tissue significantly correlated with location of the tumor in men with grade 2 cancer. Finally, we detected significant correlation between tumor location and cry1 expression in the adjacent tissue and the combined results establish that tumor influence on adjacent tissue is dependent on tumor location. Changed clock gene expression should therefore be considered in specific CRC patient sub-groups.

Circadian clock as a possible control point in colorectal cancer progression (Review)

“…Further evidence has indicated that Cry2 suppresses colon tumour growth, but the role of Cry1 in cancer progression remains controversial. Compared to matched normal mucosa, gene expression of Cry1 was reported to be upregulated in colon carcinoma tissues by three studies ( 37 , 72 , 73 ), but two other studies claimed that the expression of Cry1 did not differ significantly between groups ( 39 , 46 ). Cry2 was identified to be downregulated in CRC tissues in three studies ( 37 , 39 , 50 , 72 ).…”

Oxysterols and Gastrointestinal Cancers Around the Clock

“…Recent study examining the role of PER3 in CRC found that its overexpression enhanced fluorouracil sensitivity in CRC cells, proposing it as a potential target in CRC treatment (243). Moreover, another study showed sex-specific expression and sex-specific prognostic value of clock and clock-controlled genes, shedding light on colorectal cancer and patient characteristics that have to be taken into consideration in order to provide optimal treatment (244).…”

Dysregulation of Circadian Clock Genes Associated with Tumor Immunity and Prognosis in Patients with Colon Cancer

“…The low rate of ADCYAP1 hypermethylation in early-stage lesions and its increase with the tumor stage suggest that ADCYAP1 hypermethylation may hinder ADCYAP1's apoptotic action. Cry1 expression was increased in right colon cancers but not in left colorectum tumors [ 33 ]. CRY2NK1 upregulation is associated with a worse outcome in patients with hepatocellular cancer.…”