The Clinicopathologic and Prognostic Value of Hypoxia-Inducible Factor-2 alpha in Cancer Patients: A Systematic Review and Meta-Analysis

Hypoxia-inducible factor-2 alpha (HIF2 alpha) plays an important role in the development of tumors. However, the clinicopathologic and prognostic significance of HIF2 alpha in cancer patients remains controversial. Therefore, we performed a meta-analysis to investigate the relationship between the HIF2 alpha status and clinical outcome in human cancer. Studies were screened online using electronic databases. The pooled risk ratios or hazard ratios (HR) with their 95% confidence intervals (CI) were calculated from available publications. Subgroup analysis, sensitivity analysis, heterogeneity, and publication bias were also conducted. A total of 854 studies with 4,345 patients were obtained in this meta-analysis. The results indicated that the increased expression of HIF2 alpha could predict unfavorable overall survival of cancer patients on both univariate analysis (HR, 1.64; 95% CI, 1.41-1.92, P < 0.001) and multivariate analysis (HR, 2.21; 95% CI, 1.70-2.87, P < 0.001). Moreover, HIF2a overexpression was associated closely with tumor differentiation, tumor-node-metastasis stage, and lymph metastasis. In addition, there was no obvious evidence for significant publication bias in this meta-analysis. Our study indicated that HIF2 alpha might be an indicator of poor prognosis and clinicopathologic features of tumors and could serve as a novel biomarker in human cancer.