A Meta-Analysis of HIF-1α and Esophageal Squamous Cell Carcinoma (ESCC) Risk

To investigate the correlation of hypoxia-inducible factor-1 alpha (HIF-1 alpha) expression with clinical prognosis and efficacy of radiochemotherapy in esophageal squamous cell carcinoma (ESCC). Studies assessing the clinical or prognostic significance of HIF-1 alpha expression in ESCC published prior to December 2011 were selected by searching PubMed, EMBASE, Cochrane Library, and (China National Knowledge Infrastructure) CNKI. A meta-analysis was performed to clarify the impact of HIF-1 alpha expression on clinicopathological parameters or survival in ESCC. A total of 16 studies met the inclusion criteria, which included 1261 patients with ESCC. Accordingly, the level of HIF-1 alpha expression in esophageal tissues of patients with ESCC was significantly higher than that in normal patients (odds ratio, OR = 33.111, 95 % confidence interval, CI = 11.912-92.040). The expression of HIF-1 alpha correlated with the depth of invasion (OR = 1.701, 95 % CI = 1.076-4.705), clinical TNM stage (OR = 2.160, 95%CI = 1.516-3.077), as well as lymph node metastasis (OR = 2.393, 95 % CI = 1.319-4.344), regardless of differentiation grading (OR = 1.185, 95 % CI = 0.859-1.635). Furthermore, there was a significant association of increased HIF-1 alpha expression with poorer radiochemotherapy outcomes, 2-year overall survival (OR = 0.219, 95 % CI = 0.104-0.461) and survival (OR = 0.320, 95 % CI = 0.115-0.887, P < 0.05) in patients with ESCC. In addition, HIF-1 alpha expression correlated with VEGF expression in the ESCCs (OR = 4.635, 95%CI = 2.591-8.292). Increased expression of HIF-1 alpha plays an important role in the malignant biology of ESCC resulting in significantly poorer radiochemotherapy outcomes and 2-year overall survival. HIF-1 alpha expression may be a prognostic factor, as well as a potential target for therapy in patients with ESCC.