Clinicopathological and prognostic significance of hypoxia-inducible factor-1α in esophageal squamous cell carcinoma: a meta-analysis

Published literatures on the prognostic value of hypoxia-inducible factor-1 alpha (HIF-1 alpha) overexpression in esophageal squamous cell carcinoma (ESCC) are conflicting and heterogeneous. We performed a meta-analysis to more precisely evaluate the clinicopathological and prognostic value of HIF-1 alpha in patients with ESCC. Searches were applied to MEDLINE, Pubmed, Embase, Cochrane Library, Web of Science, and Chinese BioMedical Literature Databases until September 10, 2013, without language restrictions. The pooled hazard ratios (HRs) and odds ratios (ORs) with corresponding 95 % confidence intervals (CIs) were used to estimate the effects. Twelve studies with 942 ESCC patients were selected to evaluate the correlation between HIF-1 alpha and overall survival (OS), disease-free survival (DFS), response to chemoradiation (RC), and clinicopathological features. HIF-1 alpha overexpression was significantly associated with poor OS (HR 1.78, 95 % CI 1.41-2.24), DFS (HR 1.91, 95 % CI 1.15-3.18), and RC (HR 3.56, 95 % CI 1.68-7.53). Besides, HIF-1 alpha overexpression was significantly associated with stage (OR 2.90, 95 % CI 1.97-4.27), lymph node metastasis (OR 1.86, 95 % CI 1.39-2.49), depth of invasion (OR 2.45, 95 % CI 1.24-4.86), lymphatic invasion (OR 2.28, 95 % CI 1.46-3.56), distant metastasis (OR 2.04, 95 % CI 1.19-3.50), and vascular endothelial growth factor (OR 3.67, 95 % CI 1.81-7.46). Our results indicate that HIF-1 alpha overexpression can potently predict the poor prognosis and chemoradiation resistance for ESCC. Large prospective studies with multivariable survival analyses are now needed to confirm the clinical utility of HIF-1 alpha as an independent prognostic marker.