Abstract
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. 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. 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). 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.
Highlights
Lung cancer is one of the most common malignancies worldwide and the paramount cause of cancer deaths in the world [1]
hypoxia-inducible factor-1α (HIF-1α) is related to a differing degree of lung cancer cell, lymph node metastasis, post-operative survival time and histology (NSCLC vs. small cell lung cancer (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
Summary
Lung cancer is one of the most common malignancies worldwide and the paramount cause of cancer deaths in the world [1]. Lung cancer development is a multi-step process, driven by a series of genetic and environmental alterations. Neovascularisation and cellular adaptation to hypoxia have been recognised to be essential conditions for cancer progression. Semenza et al [3] identified the hypoxia-inducible transcription factor (HIF-1) in 1992. On the contrary, when cells are under hypoxic conditions, HIF-1α will accumulate and heterodimerise with HIF-1 β to form the transcription factor (HIF-1). Enhanced levels of HIF-1α protein have been detected in the cytoplasm and nuclei of 40% to 80% of human carcinoma cases [8]. Hypoxia-inducible factor-1α (HIF-1α), which was used as the index of hypoxia, has been evaluated for many tumours
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