Clock Gene Expression Levels and Relationship With Clinical and Pathological Features in Colorectal Cancer Patients

Abstract

The clock gene machinery controls cellular metabolism, proliferation, and key functions, such as DNA damage recognition and repair. Dysfunction of the circadian clock is involved in tumorigenesis, and altered expression of some clock genes has been found in cancer patients. The aim of this study was to evaluate the expression levels of core clock genes in colorectal cancer (CRC). Quantitative real-time polymerase chain reaction (qPCR) was used to examine ARNTL1, CLOCK, PER1, PER2, PER3, CRY1, CRY2, Timeless (TIM), TIPIN, and CSNK1? expression levels in the tumor tissue and matched apparently healthy mucosa of CRC patients. In the tumor tissue of CRC patients, compared to their matched healthy mucosa, expression levels of ARNTL1 (p=.002), PER1 (p=.002), PER2 (p=.011), PER3 (p=.003), and CRY2 (p=.012) were lower, whereas the expression level of TIM (p=.044) was higher. No significant difference was observed in the expression levels of CLOCK (p=.778), CRY1 (p=.600), CSNK1 (p=.903), and TIPIN (p=.136). As to the clinical and pathological features, a significant association was found between low CRY1 expression levels in tumor mucosa and age (p=.026), and female sex (p=.005), whereas high CRY1 expression levels in tumor mucosa were associated with cancer location in the distal colon (p?=?.015). Moreover, high TIM mRNA levels in the tumor mucosa were prevalent whenever proximal lymph nodes were involved (p= .013) and associated with TNM stages III-IV (p=.005) and microsatellite instability (p=.015). Significantly poorer survival rates were evidenced for CRC patients with lower expression in the tumor tissue of PER1 (p=.010), PER3 (p= .010), and CSNKIE (p=.024). In conclusion, abnormal expression levels of core clock genes in CRC tissue may be related to the process of tumorigenesis and exert an influence on host/tumor interactions.

Prostate cancer metastasis-driving genes: hurdles and potential approaches in their identification

“…While altered expressions of TIMELESS and DLX1 have been reported for a variety of cancers,2021222324 they have not been associated with prostate cancer metastasis. The elevated expression of TIMELESS found in our metastatic xenografts ( Table 1 ), as well as in metastatic prostate cancer patients’ samples (MSKCC cohort; Figure 2a ) and a strong correlation between elevated TIMELESS expression and poor clinical patients’ outcome (increased seminal vesicle invasion and lymph node involvement; Figure 2b ), suggest that this gene has a role in prostate cancer metastasis and perhaps as a metastasis-driving gene.…”

Overexpression of the Circadian Clock Gene Bmal1 Increases Sensitivity to Oxaliplatin in Colorectal Cancer

“…Some translational studies have explored the relationship between Bmal1 and the clinical features of patients with colorectal cancer. Previous reports have suggested that Bmal1 expression in colorectal cancer tissues is lower than that in matched healthy mucosa (44). In addition, the expression of Bmal1 and Per1 also correlates with liver metastasis and colorectal cancer outcomes (45).…”

The Role of Biological Clock in Gynecologic Cancer

“…These findings provide a mechanistic foundation for the delayed onset of tumorigenesis in clock-disrupted p53 mutant mice, giving a note of optimism in treating cancers associated with p53 mutation [37]. In humans, the expression level of TIM was higher in the tumor tissue of colorectal cancer patients, while the overexpression of the circadian clock gene BMAL1 increases sensitivity to oxaliplatin in patients with colorectal cancer [38,39]. Mazzoccoli evaluated chronodisruption in lung cancer; actually, he found that in patients with lung cancer, GH, IGF1, TRH, TSH, FT4, cortisol and IL2 values did not show rhythmic variation [40].…”