Prognostic Role of Hypoxia-Inducible Factor-2α Tumor Cell Expression in Cancer Patients: A Meta-Analysis

Hypoxia-inducible factor-2 alpha (HIF-2 alpha) plays an important role in tumor progression and metastasis. A number of studies have evaluated the correlation between HIF-2 alpha overexpression and clinical outcome in cancer patients but yielded inconsistent results. To comprehensively and quantitatively summarize the evidence on the capability of HIF-2 alpha to predict the prognosis of cancer patients with solid tumors, a meta-analysis was carried out. Renal cell carcinoma (CC-RCC) was separately analyzed due to an alternative mechanism of regulation. Systematic literature searches were performed in PubMed and Embase databases for relevant original articles until February 2018. Forty-nine studies with 6,052 patients were included in this study. The pooled hazard ratios (HRs) with corresponding confidence intervals were calculated to assess the prognostic value of HIF-2 alpha protein expression in tumor cells. The meta-analysis revealed strong significant negative associations between HIF-2 alpha expression and five endpoints: overall survival [HR = 1.69, 95% confidence interval (95% CI) 1.39-2.06], disease-free survival (HR = 1.87, 95% CI 1.2-2.92), disease-specific survival (HR = 1.57, 95% CI 1.06-2.34), metastasis-free survival (HR = 2.67, 95% CI 1.32-5.38), and progression-free survival (HR = 2.18, 95% CI 1.25-3.78). Subgroup analyses revealed similar associations in the majority of tumor sites. Overall, these data demonstrate a negative prognostic role of HIF-2 alpha in patients suffering from different types of solid tumors.