Expression of Clock Genes in Patients with Colorectal Cancer

Abstract

Recent studies have demonstrated the influence of clock genes in cell cycle regulation, cell proliferation, apoptosis and DNA damage recognition and repair. There is evidence suggesting the implication of clock genes in colorectal cancer (CRC) development and progression. The aim of this study is to evaluate the expression levels of clock genes in CRC and correlate them with patients' prognosis. Forty-two CRC samples (from 24 males and 18 females), their paired noncancerous tissues and 8 biopsies from healthy individuals were included. Quantitative real-time PCR was used to examine the expression levels of CLOCK1, BMAL1, PER1, PER2 and PER3 genes in all the samples. In the cancerous tissues CLOCK1 (p<0.0001) and BMAL1 (p<0.0001) expression levels were higher, while PER1 (p<0.0024) and PER3 (p<0.0001) expression levels were lower compared to matched healthy tissues. No difference was observed in the expression levels of PER2 (p=0.99). No correlation was found between clock gene expression and patients' clinicopathological characteristics or prognosis. The results suggest abnormal expression of CLOCK1, BMAL1, PER1 and PER3 genes in CRC but no correlation with patients' prognosis.

Expression of core clock genes in colorectal tumour cells compared with normal mucosa: a systematic review of clinical trials

“…These experimental studies suggested that Period genes control the cell cycle and act as tumour suppressors. This is consistent with the findings in this review where Period is decreased in colorectal tumours . Decreased expression of Period genes has also been reported in other types of cancer such as breast cancer , endometrial carcinoma , non‐small‐cell lung cancer , acute myeloid leukaemia , gliomas and hepatocellular carcinoma .…”

“…Bmal1 was examined in five studies . It was found to be significantly decreased in one study and significantly increased in two .…”

“…The high gene expression of Clock found in three of six studies could be connected to the decrease of Period, and thus to a decrease of the negative feedback in the autoregulatory feedback loop or individual effects of the BMAL1‐CLOCK heterodimer itself . There were limited data on survival correlated to modified core clock gene expression in colorectal cancer compared with normal mucosa.…”

Circadian Clock, Cell Division, and Cancer: From Molecules to Organism

“…This pro-proliferative effect of certain clock genes was not specific to untransformed cells, since very similar properties were also attributed to cancer cell lines. For instance, human colorectal cancers often show higher expression of Clock or Bmal1 genes compared to healthy tissue [112,113,114]. In agreement with this, overexpression of CLOCK increases proliferation of colorectal carcinoma cells in vitro and in vivo [115].…”

Deregulated expression of circadian clock genes in gastric cancer

“…It has been shown that the PER1 , PER2 , PER3 and Dec1 genes are expressed in a similar circadian manner in human peripheral blood mononuclear cells, with the peak level occurring during the habitual time of activity [35] suggesting that the oscillation of PER3 may also be an essential factor in maintaining circadian rhythm. Besides, altered PER3 expression has been reported in various cancers, including CML [19,20], HNSCC [21], HCC [18], and CRC [36]. Further investigations of PER3 function may reveal the direct links between deregulation of PER3 and prognosis in GC patients.…”