P4HA2, a key enzyme in the extracellular matrix remodeling, played a significant role in tumor progression, metastasis, and chemoresistance. While its overexpression has been associated with poor prognosis in various cancers, its overall clinical significance remained uncertain. This meta-analysis aimed to assess the prognostic value of P4HA2 and its relationship with clinicopathological features in malignancies. We systematically searched PubMed, PMC, and Web of Science for studies published up to September 2024, assessing P4HA2 expression levels in relation to overall survival (OS) and clinicopathological features. Hazard ratios (HRs) and odds ratios (ORs) were pooled using STATA software. A total of 10 studies comprising 1,203 patients were included. High P4HA2 expression was significantly associated with poor OS (HR = 1.842, 95% CI: 1.374–2.469, P < 0.001) across malignancies, particularly in solid malignancies among surgical patients (HR = 1.867, 95% CI: 1.363–2.555, P < 0.001). Elevated P4HA2 levels also correlated with lymph node metastasis (OR = 2.657, 95% CI: 1.847–3.822, P < 0.001), while no significant associations were observed for tumor invasion, TNM stage, or differentiation. Meta-regression did not identify significant sources of heterogeneity, and sensitivity and publication bias analysis confirmed the robustness of the results. P4HA2 overexpression was a strong predictor of poor OS and lymph node metastasis in malignancies, highlighting its potential as a prognostic biomarker. Further research is required to elucidate its role in tumor biology and its clinical applications.
