Pathological and prognostic significance of hypoxia-inducible factor 1α expression in epithelial ovarian cancer: a meta-analysis

Hypoxia-inducible factor-1 alpha (HIF-1 alpha) plays an important role in tumour progression and metastasis. However, the association between HIF-1 alpha and clinicopathological characteristics of epithelial ovarian cancers is controversial. We searched articles on the association between HIF-1 alpha expression and clinicopathological variables of epithelial ovarian cancer in Cochrane Library, Pubmed, Web of Knowledge and China National Knowledge Infrastructure (CNKI) from inception to February 2014. Twenty-five studies were included in the final review. The expression of HIF-1 alpha in cancer or borderline tissue was significantly higher than that in benign tissue (cancer vs. benign, odds ratio (OR) = 9.73 (95 % confidence interval (CI), 4.90, 19.32); P < 0.00001; borderline vs. benign, OR = 6.29 (95 % CI, 2.69-14.73); P < 0.0001; cancer vs. borderline, OR = 2.31 (95 % CI, 1.04, 5.09); P = 0.04). The expression of HIF-1 alpha in stages III-IV or lymph node metastasis was significantly higher than that in stages I-II or that without lymph node metastasis, respectively (OR = 3.01 (95 % CI, 1.92-4.74); P < 0.00001; OR = 5.20 (95 % CI, 2.10-12.89); P = 0.0004). HIF-1 alpha was associated with histological grade of cancer (grades 3 vs. 1, OR = 4.52 (95 % CI, 2.79-7.31); P < 0.00001; grades 3 vs. 2, OR = 2.02 (95 % CI, 1.27-3.19); P = 0.003; grades 3 vs. 1, OR = 2.43 (95 % CI), 1.65-3.59; P < 0.00001) and lower 5-year survival rates (OR = 11.46 (95 % CI, 3.43-38.29); P < 0.0001). However, histological types and the age of patients were not associated with HIF-1 alpha expression (OR = 1.01 (95 % CI, 0.72, 1.42); P = 0.94; OR = 1.06 (95 % CI, 0.73-1.55); P = 0.75). In conclusion, HIF-1 alpha is related to the malignant degree, FIGO stage, histological grade, lymph node metastasis and 5-year survival rate of epithelial ovarian cancer. It may play an important role in clinical treatment and prognostic evaluation.