Clinicopathological Characteristics of Gynecological Cancer Associated with Hypoxia-Inducible Factor 1α Expression: A Meta-Analysis Including 6,612 Subjects

Background Gynecological cancer is characterized by tumor hypoxia. However, the role of hypoxia-inducible factor 1 alpha (HIF-1 alpha) in gynecological cancer remains unclear. Method Electronic databases including Cochrane Library, PUBMED, Web of Knowledge and clinical trial registries were searched frominception through October 2014 for published, case-control studies assessing the association between HIF-1 alpha and the clinicopathological characteristics of gynecological cancer. We pooled results from 59 studies using fixed or random-effects models and present results as odds ratios (ORs) following the PRISMA guidelines. Results Our meta-analysis, which included 6,612 women, demonstrated that the expression of HIF1 alpha was associated with the clinicopathological characteristics of gynecological cancer. The expression of HIF-1 alpha in cancer or borderline tissue was significantly higher than that in normal tissue (cancer vs. normal: odds ratio (OR) = 9.59, 95% confidence interval (CI): 5.97, 15.39, p < 0.00001; borderline vs. normal: OR= 4.13, 95%(CI): 2.43, 7.02, p < 0.00001; cancer vs. borderline: OR = 2.70, 95%(CI): 1.69, 4.31, p < 0.0001). The expression of HIF-1 alpha in III. IV stage or lymph nodemetastasis was significantly higher than that in I. II stage or that without lymph node metastasis, respectively (OR= 2.66, 95%(CI): 1.87,3.79, p < 0.00001; OR= 3.98, 95% (CI): 2.10,12.89, p < 0.0001). HIF-1a was associated with histological grade of cancer (Grade 3 vs. Grade 1: OR = 3.77, 95%(CI): 2.76,5.16, p < 0.00001; Grade 3 vs. Grade 2: OR = 1.62, 95%(CI): 1.20,2.19, p = 0.002; Grade 2 vs. Grade 1: OR = 2.34, 95%(CI): 1.82,3.00, p < 0.00001), 5-years disease free survival (DFS) rates (OR = 2.93, 95%(CI): 1.43,6.01, p = 0.001) and 5-years overall survival (OS) rates (OR = 5.53, 95%(CI): 2.48,12.31, p < 0.0001). Conclusion HIF-1 alpha is associated with the malignant degree, FIGO stage, histological grade, lymph node metastasis, 5-years survival rate and recurrence rate of gynecological cancer. It may play an important role in clinical treatment and prognostic evaluation.