Prognostic value of HIF-1α in digestive system malignancies: evidence from a systematic review and meta-analysis

AIM: This meta-analysis aimed to evaluate the association of HIF-1α expression with clinicopathological features and overall survival (OS) of patients with digestive system malignancies. BACKGROUND: Numerous studies have demonstrated that hypoxia-inducible factor-1α (HIF-1α) is abnormally expressed in various solid tumors. However, the clinicopathological features and prognostic value of HIF-1α expression in patients with digestive system malignancies remain controversial. METHODS: A literature search in PubMed, Web of Science, and Scopus databases was performed to identify all relevant studies published in English until 15 October 2020. The pooled effect was calculated to evaluate the association between HIF-1α expression and clinicopathological features and overall survival in cancer patients. Pooled odds ratios (ORs) or hazard ratios (HRs) with a 95% confidence interval (CI) were calculated using fixed- or random-effects model based on between-study heterogeneity. RESULTS: A total of 44 eligible studies with 5,964 patients were included. The pooled results indicated a positive association of HIF-1α overexpression with poor overall survival (OS) (HR=1.990, 95% CI: 1.615-2.453, p<0.001) and disease-free survival (DFS) (HR=1.90, 95% CI: 1.084-3.329, p=0.043). Meta-analysis results showed that HIF-1α level expression was significantly associated with positive lymph node metastasis (OR=1.869, 95% CI: 1.488-2.248, p<0.001), distance metastasis (OR=2.604, 95% CI: 1.500-4.519, p<0.001), tumor stage (OR=1.801, 95% CI: 1.437-2.257, p<0.001) and tumor size (OR=1.392. 95% CI: 1.068-1.815, p=0.014). CONCLUSION: This meta-data suggest that HIF-1α expression might serve as an independent prognostic marker and a promising therapeutic target in patients with digestive system malignancies.