Prognostic significance of KRAS, NRAS, BRAF, and PIK3CA mutations in stage II/III colorectal cancer: A retrospective study and meta-analysis

Di Kang, Jing Li, Yangyang Li, Jingquan Xu, Jianlei Yang and Zili Zhang

PLOS ONE, 2025, vol. 20, issue 4, 1-16

Abstract: The prognostic significance of KRAS and BRAF mutations is well-established in metastatic colorectal cancer (CRC) but remains uncertain in early-stage tumors. This study retrospectively analyzed 47 stage II/III CRC patients undergoing curative surgery to assess the association of mutations in KRAS, NRAS, BRAF, and PIK3CA with overall survival (OS) and disease-free survival (DFS). Additionally, a meta-analysis was conducted to validate the prognostic relevance of these gene mutations. We included post hoc analyses of phase III randomized controlled trials (RCTs) in stage II/III patients receiving adjuvant therapy after curative resection in the meta-analysis. Pooled hazard ratio (HR) and 95% confidence interval (CI) was calculated using a random-effect model in the overall population, stratified subgroups adjusted for microsatellite instability (MSI) status, and within MSI-high (MSI-H) and microsatellite-stable (MSS) populations. In the retrospective cohort, mutations in KRAS, NRAS, BRAF, and PIK3CA were identified in 29.8%, 4.3%, 8.5%, and 14.9% of patients, respectively. No significant association between individual genes and survival was observed. However, in MSS patients, concurrent mutations were significantly associated with shorter OS and DFS (log-rank test, P

Date: 2025
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0320783

DOI: 10.1371/journal.pone.0320783

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