The Prognostic Significance of KRAS, NRAS, and BRAF Mutations in Colorectal Cancer: A Systematic Review and...

Colorectal cancer (CRC) remains a global health issue with high morbidity and mortality. According to molecular profiling, genetic mutations such as KRAS, NRAS, and BRAF play a significant role in tumor biology, treatment effectiveness, and patient prognosis. The exact effect of these alterations on overall survival (OS) is, however, unclear. This systematic review and meta-analysis estimated the combined effect of KRAS, NRAS, and BRAF mutations on CRC survival relative to wild-type tumors.

This study focused on research conducted in the last decade and was registered on PROSPERO (Reg No: CRD420251003000). Search was done using PubMed, EMBASE, MEDLINE, and Google Scholar. Cohort, case control, and randomized controlled trials reporting Overall Survival Hazard Ratios (HRs) for CRC patients with and without KRAS, NRAS, or BRAF mutations were considered. Multiple reviewers independently extracted and assessed data quality using the Newcastle-Ottawa Scale. For heterogeneity, pooled HRs were computed using a random-effects model. Publication bias was determined by funnel plot asymmetry.

Nine trials with 3096 participants qualified. Compared to wild-type CRC, KRAS, NRAS, and BRAF mutations were substantially linked with lower overall survival (pooled HR > 1, P < .05). KRAS mutations were most common and consistently associated with poor survival, while BRAF mutations had the largest impact. Mild funnel plot asymmetry suggested publication bias, but risk-of-bias assessment showed moderate to high methodological quality across trials.

This meta-analysis shows that KRAS, NRAS, and BRAF mutations are important for adverse prognostic markers in colorectal cancer, linked to reduced overall survival. Routine molecular testing for these mutations is vital to enable personalized treatment, improve patient stratification, and enhance clinical outcomes in colorectal cancer management.