Clinicopathological and prognostic significance of hypoxia-inducible factor-1 alpha in lung cancer: a systematic review with meta-analysis

Hypoxia-inducible factor-1 alpha (HIF-1 alpha) plays a vital role in the initiation, evaluation and prognosis in lung cancer. The prognostic value of HIF-1 alpha reported in diverse study remains disputable. Accordingly, a meta-analysis was implemented to further understand the prognostic role of HIF-1 alpha in lung cancer. The relationship between HIF-1 alpha and the clinicopathological characteristics and prognosis of lung cancer were investigated by a meta-analysis. PubMed and Embase were searched from their inception to January 2015 for observational studies. Fixed-effects or random-effects meta-analyses were used to calculate odds ratios and 95% confidence intervals of different comparisons. A total of 20 studies met the criteria. The results showed that HIF-1 alpha expression in lung cancer tissues was significantly higher than that in normal lung tissues. Expression of HIF-1 alpha in patients with squamous cell carcinoma was significantly higher than that of patients with adenocarcinomas. Similarly, non-small cell lung cancer (NSCLC) patients had higher HIF-1 alpha expression than small cell lung cancer (SCLC) patients. Moreover, lymph node metastasized tissues had higher HIF-1 alpha expression than non-lymph node metastasized tissues. A high level HIF-1 alpha expression was well correlated with the expression of vascular endothelial growth factor and epidermal growth factor receptor in the NSCLC. Notably, NSCLC or SCLC patients with positive HIF-1 alpha expression in tumor tissues had lower overall survival rate than patients with negative HIF-1 alpha expression. It was suggested that HIF-1 alpha expression may be a prognostic biomarker and a potential therapeutic target for lung cancer.