Abstract
BackgroundColorectal 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.MethodsThe 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.ResultsOur 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.ConclusionAnalysis 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.
Highlights
Colorectal cancer is considered as an important public health issue since it is the third most common malignancy type diagnosed, with more than 1.3 million new cases and 690 thousand deaths worldwide in 2012 [1]
Our results showed that protection of telomeres 1 (POT1), ATR, Chk1 and Chk2 show increased expression in CRC relative to the adjacent mucosa
There was a positive correlation between the age of the patients and hTERT expression
Summary
Colorectal cancer is considered as an important public health issue since it is the third most common malignancy type diagnosed, with more than 1.3 million new cases and 690 thousand deaths worldwide in 2012 [1]. In the Kingdom of Saudi Arabia (KSA), CRC is the leading cause of cancer-related deaths, representing 12% of all cancers and accounting for more than 11% of all cancer cases [1]. The etiological and risk factors of CRC development are variable reflecting the multifactorial nature of the disease. Several risk factors are shown to be associated with CRC development. One of the factors is age, where individual older than 50 years have a higher risk of developing CRC [8]. Another factor contributing to CRC is inflammatory bowel disease [9]. Colorectal cancer is the leading cause of cancer-related deaths in Saudi Arabia. The present study examined their contributions to colorectal cancer progression in Saudi patients.
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