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

Purpose: Hypoxia-inducible factor-2α (HIF-2α) plays an important role in the development of tumors. However, the clinicopathological and prognostic significance of HIF-2α in cancer patients remains controversial. Therefore, we performed a meta-analysis to investigate the relationship between the HIF-2α status and clinical outcome in human cancer. Methods: Studies were screened online using electronic databases. The pooled risk ratios (RRs) or hazard ratios (HRs) with their 95% confidence intervals (95% CIs) were calculated from available publications. Subgroup analysis, sensitivity analysis, heterogeneity, and publication bias were also conducted. Results: A total of 854 studies with 4345 patients were obtained in this meta-analysis. The results indicated that the increased expression of HIF-2α could predict unfavorable overall survival (OS) 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, HIF-2α overexpression was associated closely with tumor differentiation, tumor-node-metastasis (TNM) stage and lymph metastasis. In addition, there was no obvious evidence for significant publication bias in this meta-analysis. Conclusions: Our study indicated that HIF-2α might be an indicator of poor prognosis and clinicopathological features of tumors, and could be served as a novel biomarker in human cancer.