Funnel plot.

Funnel plot of the estimation of publication bias on the effect of PIK3CA exon 9 and exon 20 mutations on survival outcomes of endometrial cancer patients. (DOCX)</p

Characteristics of patients enrolled in included studies.

Characteristics of patients enrolled in included studies.</p

Meta-analysis results of the effect of <i>PIK3CA</i> mutations on EC patient survival in relation to grade.

Forest plots visualizing relative risks (RR) of combined overall and disease-specific survival in the a) low-grade and b) high grade subgroups.</p

PRISMA flowchart of included and excluded literature.

Studies were identified using keyword-based searches in the following databases: CENTRAL, MEDLINE, Embase and Web of Science in the primary search. In addition, publications were manually curated from the COSMIC sequencing database.</p

Meta-analysis results of the effect of <i>PIK3CA</i> mutations on EC patient survival.

Forest plot visualizing relative risks (RR) of combined overall and disease-specific survival among studies included. Grey boxes represent relative risk of individual studies, with box size representing the inverse of the variance in individual studies and vertical black lines representing 95% confidence intervals. The diamonds represent the summarized effect of the PIK3CA mutation on survival for both the common effects and random effects models.</p

Quality assessment of the included studies according to the Newcastle-Ottawa Scale.

Quality assessment of the included studies according to the Newcastle-Ottawa Scale.</p

Modified Newcastle-Ottawa quality assessment scale and scoring algorithm.

Modified Newcastle-Ottawa quality assessment scale and scoring algorithm.</p

PRISMA 2009 checklist.

Several studies have highlighted the frequent alterations of the PI3K pathway in endometrial cancer leading to increased signaling activation with potential for targeted treatment. The objective of this meta-study was to evaluate how PIK3CA exon 9/20 mutations affect survival in endometrial cancer patients, based on available literature. Topic-based search strategies were applied to databases including CENTRAL, MEDLINE, Embase, Web of Science and COSMIC. All studies assessing the impact of mutations in exon 9 and exon 20 of PIK3CA on survival rates of endometrial cancer patients were selected for inclusion. Statistical meta-analysis was performed with the ‘meta’ package in RStudio. Overall, 7 of 612 screened articles were included in the present study, comprising 1098 women with endometrial cancer. Meta-analysis revealed a tendency of impaired survival for patients with PIK3CA exon 9 and/or exon 20 mutations (RR 1.28; 95% CI 0.84, 1.94; p = 0.25). This tendency was consistent in subgroup analyses stratified by histologic type or -grade, with the most prominent effect in low-grade endometrial cancers (RR 2.04; 95% CI 0.90, 4.62; p = 0.09). In summary, these results suggest that PIK3CA mutations negatively influence survival outcomes of patients with endometrial cancer, including those with low-grade tumors.</div

Summary of included studies.

Several studies have highlighted the frequent alterations of the PI3K pathway in endometrial cancer leading to increased signaling activation with potential for targeted treatment. The objective of this meta-study was to evaluate how PIK3CA exon 9/20 mutations affect survival in endometrial cancer patients, based on available literature. Topic-based search strategies were applied to databases including CENTRAL, MEDLINE, Embase, Web of Science and COSMIC. All studies assessing the impact of mutations in exon 9 and exon 20 of PIK3CA on survival rates of endometrial cancer patients were selected for inclusion. Statistical meta-analysis was performed with the ‘meta’ package in RStudio. Overall, 7 of 612 screened articles were included in the present study, comprising 1098 women with endometrial cancer. Meta-analysis revealed a tendency of impaired survival for patients with PIK3CA exon 9 and/or exon 20 mutations (RR 1.28; 95% CI 0.84, 1.94; p = 0.25). This tendency was consistent in subgroup analyses stratified by histologic type or -grade, with the most prominent effect in low-grade endometrial cancers (RR 2.04; 95% CI 0.90, 4.62; p = 0.09). In summary, these results suggest that PIK3CA mutations negatively influence survival outcomes of patients with endometrial cancer, including those with low-grade tumors.</div

Meta-analysis results of the effect of <i>PIK3CA</i> mutations on EC patient survival related to histologic type.

Forest plots of the relative risks (RR) of combined overall and disease-specific survival in a) endometrioid and b) non-endometrioid subgroups.</p