Background: Hypoxia-inducible factor-1α (HIF-1α) plays an important role in tumour progression and metastasis through activation of many _target genes that are especially involved in pivotal aspects of cancer biology. However, the prognostic role of HIF-1α has been controversial in primary patients with lung cancer. This meta-analysis was performed to systematically evaluate whether HIF-1α expression is associated with the clinical outcomes in lung cancer patients.

Methods: We retrieved relevant articles from Cochrane library, PubMed, EMbase, CNKI, CBM, VIP and Wan Fang Databases from inception to May 2012. Studies were selected using specific inclusion and exclusion criteria. A systematic review and meta-analysis was performed on the association between HIF-1α expression and clinical outcomes in lung cancer patients. All analyses were performed using the Revman 5.1 software.

Results: A total of 30 studies were identified as eligible for the systematic review and meta-analysis. The expression of HIF-1α was significantly higher than those in normal lung tissue; and III-IV stage, lymph node metastasis, poorly differentiation, squamous cell carcinoma and small cell lung cancer (SCLC) were significantly higher than those in I-II stage, no lymph node metastasis, well differentiation, adenocarcinomas and non small cell lung cancer (NSCLC), respectively (odds ratio (OR) = 19.00, 95% confidence interval (CI):12.12-29.78, p <0.00001; OR = 0.23, 95% CI:0.14-0.36, p <0.00001; OR = 3.72, 95% CI:2.38-5.80, p <0.00001; OR = 0.47, 95% CI:0.31-0.70, p <0.00002, OR = 0.24, 95% CI:0.07-0.77, p = 0.02; OR = 0.78, 95% CI:0.63-0.98, p = 0.03). VEGF and CA IX positive expression in HIF-1α positive tumour tissues were significantly higher than those in HIF-1α negative tumour tissues, respectively (OR = 3.23, 95% CI: 1.90-5.46, p <0.0001; OR = 3.84, 95% CI: 2.10-7.03, p <0.0001). The positive HIF-1α tumour tissues of patients had lower 5-year survival rates (OR = 0.13, 95% CI: 0.03-0.47, p = 0.002) and overall survival (relative risk (RR) = 1.68, 95% CI: 1.12-2.50, p = 0.01).

Conclusions: HIF-1α is related to a differing degree of lung cancer cell, lymph node metastasis, post-operative survival time and histology (NSCLC vs. SCLC, adenocarcinomas vs. squamous cell carcinoma). HIF-1 α , which combines other proteins, such as vascular endothelial growth factor (VEGF) or CA IX, might serve as important parameters in evaluating biological behaviour and prognosis of lung cancer; it will be of benefit to clinical treatment and prognostic evaluation.