Clinicopathological and prognostic value of hypoxia-inducible factor-1α in patients with bone tumor: a systematic review and meta-analysis

Abstract

Abstract Background Recently, many studies have shown the role of hypoxia-inducible factor-1α (HIF-1α) expression in the outcome of bone tumor. However, the results remain inconclusive. It is necessary to carry out a meta-analysis of all the current available data to clarify the relationship between HIF-1α and survival or clinicopathological features of bone tumor. Methods PubMed, Cochrane Library, Web of Science, China National Knowledge Internet, and Wanfang databases were used to search the relationship between HIF-1α and bone tumor. Articles investigating clinicopathological and prognostic value of HIF-1α in bone tumor patients were enrolled in this meta-analysis. Overlapping articles, duplicate data, reviews, case reports, and letters without original data were excluded. The pooled risk ratios (RRs) and hazard ratios (HRs) were used to evaluate the clinicopathological and prognostic value of HIF-1α on bone tumor patients, respectively. Results A total of 28 studies including 1443 patients were included in this meta-analysis, which were involved in three different types of bone tumor including 3 chondrosarcomas, 2 giant cell tumors of bone, and 23 osteosarcomas. Our results showed that high expression levels of HIF-1α were associated with poorer OS (overall survival) (HR = 2.61, 95% CI 2.11–3.23, P < 0.001) and shorter DFS (disease-free survival) (HR = 2.02, 95% CI 1.41–2.89, P < 0.001) in bone tumor. In addition, this study also analyzed the role of HIF-1α expression in clinicopathological features, which were closely related with the severity of bone tumor, including differentiation, clinical stage, metastasis, and microvessel density. Our results indicated that HIF-1α overexpression was significantly associated with differentiation (RR = 1.56, 95% CI 1.00–2.43, P = 0.049), clinical stage (RR = 1.75, 95% CI 1.25–2.45, P = 0.001), metastasis (RR = 1.78, 95% CI 1.58–2.00, P < 0.001), and microvessel density (SMD = 2.34, 95% CI 1.35–3.34, P < 0.001) of bone tumor. Conclusions HIF-1α overexpression indicated an unfavorable factor for OS and DFS in bone tumor, suggesting that HIF-1α may serve as a potential prognostic marker for bone tumor.

Keywords

• Hypoxia-inducible factor-1α
• Bone tumor
• Prognosis
• Clinicopathological characteristics
• Meta-analysis