AUTHOR=Moreno Roig Eloy , Yaromina Ala , Houben Ruud , Groot Arjan J. , Dubois Ludwig , Vooijs Marc TITLE=Prognostic Role of Hypoxia-Inducible Factor-2α Tumor Cell Expression in Cancer Patients: A Meta-Analysis JOURNAL=Frontiers in Oncology VOLUME=8 YEAR=2018 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2018.00224 DOI=10.3389/fonc.2018.00224 ISSN=2234-943X ABSTRACT=

Hypoxia-inducible factor-2α (HIF-2α) plays an important role in tumor progression and metastasis. A number of studies have evaluated the correlation between HIF-2α overexpression and clinical outcome in cancer patients but yielded inconsistent results. To comprehensively and quantitatively summarize the evidence on the capability of HIF-2α 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-2α protein expression in tumor cells. The meta-analysis revealed strong significant negative associations between HIF-2α 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-2α in patients suffering from different types of solid tumors.