Prognostic Value of KRAS Mutations in Colorectal Cancer Patients.

Abstract

Simple SummaryKirsten rat sarcoma viral oncogene homolog (KRAS)-mutated colorectal cancer (CRC) seems to have a different biological behavior and therapeutic approach compared with non-KRAS mutated CRC. Except for the proven predictive significance of KRAS mutations in CRC patients, their prognostic significance is still under evaluation. Our study shows that 93.2% of RAS-mutated patients were KRAS mutants, with G12D being the most common subtype. KRAS G12D mutation is correlated with better overall survival (OS). KRAS G12C mutations may indicate worse prognosis regarding progression free (PFS) and OS, as well as exon 4 and exon 3 KRAS mutations for PFS and OS, respectively. Further studies are warranted to confirm these results.Colorectal cancer (CRC) remains a major public health issue. The detection of parameters that affect CRC prognosis is of great significance. KRAS mutations, play a crucial role in tumorigenesis with a strong predictive value. KRAS-mutated stage-IV CRC patients gain no benefit of the anti-EGFR therapy. The KRAS G12C mutation subtype is under investigation for treatment regimens. The present study aimed to detect various RAS mutations in a cohort of 578 RAS-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. KRAS mutations were detected in 93.2% of patients, with KRAS G12D being the most common subtype (30.1%). KRAS mutations presented shorter progression-free (PFS) and overall survival (OS), compared with NRAS mutations, although not significantly (PFS: 13.8 vs. 18.5 months; p = 0.552; OS: 53.1 vs. 60.9 months; p = 0.249). KRAS G12D mutations presented better OS rates (p = 0.04). KRAS G12C mutation, even though not significantly, presented worse PFS and OS rates. KRAS exon 3 and 4 mutations presented different PFS and OS rates, although these were not significant. Concluding, KRAS G12D and G12C mutations lead to better and worst prognosis, respectively. Further studies are warranted to validate such findings and their possible therapeutic implication.