The Effect of KRAS and NRAS Variants on the Prognosis of Colorectal Cancer among the Western Saudi Population

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.