Prognostic Value of KRAS Mutations in Colorectal Cancer Patients

Abstract

Colorectal cancer (CRC) remains a major public health issue. The detection of parameters that affect CRC prognosis is of great significance. <i>KRAS</i> mutations, play a crucial role in tumorigenesis with a strong predictive value. <i>KRAS</i>-mutated stage-IV CRC patients gain no benefit of the anti-EGFR therapy. The <i>KRAS</i> G12C mutation subtype is under investigation for treatment regimens. The present study aimed to detect various <i>RAS</i> mutations in a cohort of 578 <i>RAS</i>-mutated CRC patients; 49% of them had de novo metastatic disease; 60% were male; 71.4% had left-sided tumors; and 94.6% had a good performance status. <i>KRAS</i> mutations were detected in 93.2% of patients, with <i>KRAS</i> G12D being the most common subtype (30.1%). <i>KRAS</i> mutations presented shorter progression-free (PFS) and overall survival (OS), compared with <i>NRAS</i> mutations, although not significantly (PFS: 13.8 vs. 18.5 months; <i>p</i> = 0.552; OS: 53.1 vs. 60.9 months; <i>p</i> = 0.249). <i>KRAS</i> G12D mutations presented better OS rates (<i>p</i> = 0.04). <i>KRAS</i> G12C mutation, even though not significantly, presented worse PFS and OS rates. <i>KRAS</i> exon 3 and 4 mutations presented different PFS and OS rates, although these were not significant. Concluding, <i>KRAS</i> G12D and G12C mutations lead to better and worst prognosis, respectively. Further studies are warranted to validate such findings and their possible therapeutic implication.