Impact of RAS/RAF mutations on clinical and prognostic outcomes in metastatic colorectal cancer
Abstract
Introduction:
Early activation of RAS/RAF mutations is a key molecular feature in colorectal cancer (CRC), with these mutations being proposed as both predictive and prognostic biomarkers. This longitudinal study aimed to analyze the genotypic variations in metastatic CRC (mCRC) and explore their associations with disease prognosis and clinicopathological features. The study was conducted over three years (2016–2018) at two major referral hospitals affiliated with Tabriz University of Medical Sciences.
Methods:
A total of 173 mCRC cases were analyzed for KRAS, NRAS, and BRAF mutations using Idylla assays on surgically resected or biopsied tissue samples. The Cox proportional hazards model was applied in two stages to identify factors influencing overall survival (OS) and to calculate hazard ratios (HRs) with 95% confidence intervals (CIs).
Results:
The observed 1- to 5-year OS rates were 78%, 65%, 55%, 46%, and 42%, respectively. KRAS mutations in codon 12 emerged as an independent prognostic factor, with affected patients showing significantly lower OS (P for Log-rank = 0.049) and an increased risk of mortality (HR = 2.30; 95% CI: 0.95–5.58; P = 0.066). Additionally, liver metastasis (HR = 2.49; 95% CI: 1.49–12.52; P = 0.002) and tumors located in the distal colon (HR = 3.36; 95% CI: 1.07–10.49; P = 0.037) were associated with poorer prognosis.
Conclusion:
KRAS codon 12 mutations represent an independent and significant adverse prognostic marker in mCRC. Patients with liver metastases or distal colon tumors also face a poorer outlook. Routine testing for oncogenic Lifirafenib mutations may enhance prognosis assessment and guide more effective management strategies.