EXPLORING THE PROGNOSTIC VALUE OF COMBINED MSI AND KRAS/BRAF MUTATIONAL STATUS IN COLORECTAL CANCER PATIENTS

Background: Colorectal cancer (CRC) is a significant global health concern, and constant improvement in treatment and prediction is needed. Though resection with adjuvant therapy is the standard for resectable CRC, optimal patient benefit and the development of individualized strategies remain relevant. Microsatellite Instability (MSI) has emerged as a significant molecular marker but requires more definitive clarification of its prognostic interaction with other mutations like BRAF and KRAS. Objective: The objective of this meta-analysis was to comprehensively assess the prognostic value of MSI status, as well as KRAS and BRAF mutations, on overall survival (OS) and progression-free survival (PFS) in patients with CRC after surgical resection. Methods: Systematic literature review was performed, and research was identified on the basis of predefined eligibility criteria. Data for OS, PFS, MSI status, and KRAS/BRAF mutation were gathered. Fixed-effect meta-analysis was conducted to calculate summary HRs and 95% CIs. Risk bias was assessed using standardized tools, and publication bias was tested. Results: The meta-analysis revealed that MSI-high (MSI-H) status was also significantly associated with improved OS (HR: 0.68, 95% CI: 0.60 - 0.77; p<0.05) and improved PFS (HR: 0.70, 95% CI: 0.53 - 0.94; p<0.05) compared to microsatellite stable/low (MSS/MSI-L) tumors. Conversely, the presence of a BRAF mutation was significantly associated with poorer OS (HR: 1.48, 95% CI: 1.20 - 1.83; p<0.05). KRAS mutational status was not found to have a statistically significant independent association with either OS (HR: 1.18, 95% CI: 0.98 - 1.42) or PFS (HR: 1.10, 95% CI: 0.92 - 1.32) in this pooled analysis. BRAF mutation was not found to have an impact on PFS (HR: 1.02, 95% CI: 0.84 - 1.25). No publication bias was detected to be significant. Conclusion: This meta-analysis shows compelling evidence that MSI-H status is an independent favorable prognostic marker for OS and PFS in patients with resected CRC. By contrast, BRAF mutation is a potent indicator of poor OS. These findings underscore the significance of standard molecular profiling, and particularly MSI and BRAF status, to more accurately refine prognostic stratification and potentially impact personalized adjuvant treatment decisions in CRC therapy. Further research into the individual subtypes of KRAS mutations and their interaction with MSI status is required.