KRAS/NRAS/BRAF mutational profile and association with clinicopathological characteristics in patients with metastatic colorectal cancer

Colorectal cancer (CRC) is increasingly prevalent in Jordan and poses a significant public health challenge. The presence of Kirsten rat sarcoma viral oncogene homolog (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS) and v-Raf Murine Sarcoma Viral Oncogene Homolog B (BRAF) mutations is key in CRC diagnostics, as these mutations are associated with resistance to monoclonal antibodies targeting the epidermal growth factor receptor. The present study aimed to identify these mutations in patients with CRC and assess their associations with clinicopathological characteristics. A retrospective analysis was conducted using data from 262 patients with metastatic CRC (mCRC) at the Jordanian Military Cancer Center-Royal Medical Services (Amman, Jordan). Variables such as age, sex, tumor differentiation and the mutational status of KRAS, NRAS and BRAF, along with tumor location, were analyzed statistically to explore associations between mutations and tumor characteristics. Among the included patients, 48.5% had KRAS mutations, 3.8% had NRAS mutations and 0.8% had BRAF mutations. The majority of KRAS mutations were in exon 2 at codons 12 and 13, with the highest mutational rate at 45.8%. In the univariate model, NRAS mutations were significantly associated with moderately differentiated tumors and the multivariate hierarchical regression analysis established that KRAS mutations were significantly associated with histological subtypes [mucinous adenocarcinoma, tubular adenocarcinoma, signet adenocarcinoma and adenocarcinoma (not specified)]. These results highlighted the molecular profiles and clinicopathological characteristics of patients with mCRC, which demonstrated the associations between mutational status and the varying clinicopathological aspects based on the type of RAS mutation. Thus, these specific traits (patient's age, sex, CRC site, histological subtypes and tumor grade) may be taken into account when evaluating the predictive significance of RAS and BRAF status in CRC and tailored treatment strategies.