<i>PIK3CA</i> mutation and clinicopathological features of colorectal cancer: a systematic review and Meta-Analysis

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