Association of KRAS, NRAS, and BRAF Mutations with Clinicopathologic Characteristics in Algerian Colorectal Cancer Patients

Abstract

     We conducted a study investigating the mutational profiles of KRAS, NRAS, and BRAF biomarkers in metastatic colorectal cancer (mCRC) patients and their correlation with clinicopathologic characteristics. Our study aimed to identify the primary cause of acquired resistance to anti-EGFR treatment in mCRC patients and to investigate the frequency and distribution of KRAS, NRAS, and BRAF mutations in mCRC patients.

We employed real-time PCR and direct sequencing for molecular biology analysis and immunohistochemistry to determine Micro Satellite Instability (MSI) status. Using XLSTAT software (version 2016.02.28451), we evaluated statistical tests. We found that KRAS, NRAS, and BRAF mutations were present in 48.7%, 5.54%, and 7.19% of the cases, respectively, with G12D, G12V, and G13D being the most common KRAS mutation subtypes identified. KRAS and BRAF mutations were more frequent in elderly patients and the left colon (p=0.004 vs. p=0.04 and p=0.001 vs. p>0.0001, respectively) and were significantly associated with a well-differentiated histological type (p=0.001 vs. p=0.02). However, we could not establish a significant relationship between NRAS mutation, MSIs, and patient-specific characteristics. Our study revealed that mutations in KRAS occurred more frequently outside of exon 2, and the left colon was the predominant location for mutations in both KRAS and BRAF.

Our findings could help oncologists identify prognostic and predictive biomarkers for selecting appropriate targeted patient therapies. Colorectal cancer is prevalent worldwide, and molecular epidemiology is increasingly crucial in personalized medicine.