Impact of RAS/RAF mutations on clinical and prognostic outcomes in metastatic colorectal cancer

Introduction: Early-activated RAS/RAF mutation status is a key molecular finding in colorectal cancer (CRC), while these mutations have been proposed as predictive and prognostic biomarkers. The present study has been designed as a longitudinal study to evaluate and summarize the different genotypes of metastatic CRC (mCRC), and assessing any association with the disease prognosis and clinicopathological characteristics. This study was performed in two main referral hospitals of Tabriz University of Medical Sciences, over three years (2016-2018). Methods: Mutations were detected by Idylla tests of KRAS/NRAS/BRAF among a total of 173 mCRCs, using surgically-resected specimens or biopsied samples. To evaluate the factors associated with overall survival (OS) and prognosis, the Cox proportional hazards model was used in two steps to estimate the outcome measures (hazard ratio, or HR) with a 95% confidence interval (CI). Results: The nominal 1 to 5-year OS rates were 78%, 65%, 55%, 46%, and 42%, respectively. KRAS mutations in codon 12 was an independent significant prognostic factor, as the patients with codon 12 mutations had a significantly lower OS (P Log-rank=0.049) and a higher hazard of mortality (HR=2.30; 95% CI: 0.95-5.58; P =0.066). Also, the mCRC patients with liver metastasis (HR=2.49; 95% CI: 1.49-12.52; P =0.002) and tumors of the distal colon (HR=3.36; 95% CI: 1.07-10.49; P =0.037) had a significantly worse prognosis. Conclusion: KRAS mutation in codon 12 was an independent significant poor prognostic factor, and patients with liver metastasis had a significantly worse prognosis. Routinely performing specific oncogenic tests may help improve the patients' prognosis and life expectancy.