PIK3CA mutation and clinicopathological features of colorectal cancer: a systematic review and Meta-Analysis.

ABSTRACT

Background: There is conflicting evidence regarding the association between PIK3CA mutations and clinicopathological features of colorectal cancer (CRC). We performed a comprehensive meta-analysis investigating the association between PIK3CA mutations and clinicopathological features in CRC, including subgroup analysis of mutations in exons 9 and 20, to elucidate the role of PIK3CA mutations in CRC.Materials and Methods: A detailed literature search was performed within the PubMed, Web of Science, and Embase databases, examining the associations between PIK3CA mutations and demographic characteristics, clinicopathologic parameters, and molecular features in patients with CRC. The odds ratios with 95% confidence intervals were used to estimate the effect of PIK3CA mutations on outcome parameters.Results: Forty-four studies enrolling 17621 patients were eligible for inclusion. PIK3CA mutations were associated with proximal tumor location, mucinous differentiation, KRAS mutations, and microsatellite instability (MSI). Subgroup analysis demonstrated that PIK3CA exon 9 mutations were positively associated with proximal tumor location and KRAS mutations, and negatively associated with BRAF mutations and MSI; exon 20 mutations were associated with proximal tumor location, KRAS mutations, BRAF mutations and MSI.Conclusions: Our findings suggest that overall or exon-specific PIK3CA mutations showed null associations with key clinicopathological parameters, including disease stage and tumor differentiation, indicating that PIK3CA mutations do not predict aggressive clinicopathological characteristics in CRC. As PIK3CA mutations were found to be closely associated with KRAS mutations, their relationship warrants further investigation. Since PIK3CA exon 9 and 20 mutations showed different tendencies with regard to BRAF mutation and MSI status, they may have distinct molecular impacts on CRC.