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Background  Colorectal cancer is the leading cause of cancer-related deaths in Saudi Arabia. Cancer has a multifactorial nature and can be described as a disease of altered gene expression. The profiling of gene expression has been used to identify cancer subtypes and to predict patients’ responsiveness. Telomere-associated proteins that regulate telomere biology are essential molecules in cancer development. Thus, the present study examined their contributions to colorectal cancer progression in Saudi patients.    Methods  The expression of  hTERT ,  TRF1 ,  TRF2 ,  POT1 ,  ATR ,  ATM ,  Chk1  and  Chk2  were measured via real-time PCR in matched cancerous and adjacent tissues of CRC patients. The protein level of hTERT, TRF1, TRF2, ATR, ATM, Chk1 and Chk2 were measured using immunohistochemistry. A region of  hTERT  core promoter was sequenced via Sanger sequencing. Methylation of CTCF binding site was examined via methylation-specific PCR. Finally, the length of telomere was estimated using q-PCR.    Results  Our results showed that  POT1 ,  ATR ,  Chk1 and Chk2  show increased expression in CRC relative to the adjacent mucosa. The expression levels of each gene were associated with clinicopathological characteristics of patients with CRC. There was a positive correlation between the age of the patients and  hTERT  expression. Regarding tumor site, telomere length,  ATR ,  ATM  and  Chk1  were shown to be altered. No somatic mutation was detected in  hTERT  core promoter, and no differences in methylation patterns at CTCF binding site in the promoter between normal and cancer tissues.    Conclusion  Analysis of targeted genes expression in colorectal cancer based on the clinical variables revealed that tumor location and age could have a role in gene expression and telomere length variations and this could be taken under consideration during CRC diagnosis and therapy. Other epigenetic mechanisms could influence  hTERT  expression in cancers. Our findings warrant further validation through experiments involving a larger number of patients.

The expression of telomere-related proteins and DNA damage response and their association with telomere length in colorectal cancer in Saudi patients