Abstract
Colorectal Cancer (CRC) is one of the most common cancer with high mortality rate globally and the second leading cancer in Saudi Arabia. RAS oncogenes play critical roles in the regulation of the cellular function and any mutation in these genes leads to develop CRC. Therefore, we identified the most common mutations in KRAS and NRAS genes by applying next generation sequencing (NGS) then, we assessed the correlation between these mutations and the clinicopathological features. KRAS-mutated carcinoma was significantly associated in patients who were older than 60 years old (83.3% vs 16.7%, P = 0.039) and it was associated with female patients as well, (83.3% vs 30%, P = 0.039). Also, KRAS-mutated carcinoma was significantly associated with mucinous differentiation (85.7% vs 14.3%; P = 0.012) and higher tumor grade (P = 0.014). In addition, the number of KRAS mutations per case was significantly associated with depth of the invasion (p = 0.049). The most common mutation was a missense mutation and it was highly associated with age and gender (both, p = 0.039). Also, it was highly associated with tumor grade and with mucinous differentiation (p = 0.014, p = 0.012), respectively. On the other hand, NRAS mutated carcinoma was associated only with distant metastasis however, this association was not significant (p = 0.064). For overall survival, KRAS-mutated carcinomas had a significantly worse overall survival (p = 0.025). While, no significant association was between NRAS mutation and overall survival (p = 0.985). We believe that KRAS and NRAS genes can be prognostic factors for CRC patients and the information obtained may contribute for better diagnosis and therapeutic effect.
Highlights
Colorectal Cancer (CRC) is the second leading cancer type of the estimated number of new cancer cases in 2016 in Saudi Arabis (12.6%) (Saudi Cancer registry, 2016) for both genders
KRAS-mutated carcinoma was significantly associated in patients who were older than 60 years old (83.3% vs 16.7%, P = 0.039) and it was associated with female patients as well, (83.3% vs 30%, P = 0.039)
We investigated 16 patients with CRC by applying generation sequencing in the population of the western region of the Saudi Arabia
Summary
Colorectal Cancer (CRC) is the second leading cancer type of the estimated number of new cancer cases in 2016 in Saudi Arabis (12.6%) (Saudi Cancer registry, 2016) for both genders. The progression of the molecular level in the tumor cells will cause genetic instability and genetics defect which leads to the development of sporadic CRC. 60% of CRC caries mutations in the RAS oncogene, either KRAS, NRAS or both. The most commonly reported mutation in the KRAS gene is located on exon 2 and changes the codons 12 and codon 13. The most commonly reported mutation in the KRAS gene is located on exon 2 and changes the codons and codon Another frequently reported mutation in codon 16 and 146 have been reported, it has lower effect on the development of the tumor cells. The most commonly reported mutation in the NRAS gene is located in codon 61 and 12 [7] [8]. Activating mutations in the KRAS gene has been found to be predictor of response to EGFR-targeted therapies, examining the KRAS and NRAS mutations are an essential step in clinical diagnosis and proper treatment
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