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Meta-Analysis
. 2021 Jun;36(6):1487-1496.
doi: 10.1111/jgh.15395. Epub 2021 Jan 26.

Effects of hypoxia-inducible factor-1α and hypoxia-inducible factor-2α overexpression on hepatocellular carcinoma survival: A systematic review with meta-analysis

Zi-Niu Ding  1 , Zhao-Ru Dong  1 , Zhi-Qiang Chen  1 , Ya-Fei Yang  1 , Lun-Jie Yan  1 , Hai-Chao Li  1 , Kai-Xuan Liu  1 , Cheng-Yu Yao  1 , Yu-Chuan Yan  1 , Chun-Cheng Yang  1 , Tao Li  1
Affiliations
Meta-Analysis

Effects of hypoxia-inducible factor-1α and hypoxia-inducible factor-2α overexpression on hepatocellular carcinoma survival: A systematic review with meta-analysis

Zi-Niu Ding et al. J Gastroenterol Hepatol. 2021 Jun.

Abstract

Background and aim: The role of hypoxia-inducible factor-1α (HIF-1α) and hypoxia-inducible factor-2α (HIF-2α) has been implicated in the clinical prognosis of hepatocellular carcinoma (HCC), but the results remain controversial. We aim to investigate the association of HIF-1α and HIF-2α overexpression with the prognosis and clinicopathological features of HCC.

Methods: A systematic search was conducted in PubMed, Embase, Scopus, Web of Science, and Cochrane Library until June 20, 2020. Meta-analysis was conducted to generate combined HRs with 95% confidence intervals (CI) for overall survival (OS) and disease-free survival (DFS). Odds ratios (ORs) with 95% CI were also derived by fixed or random effect model.

Results: Twenty-two studies involving 3238 patients were included. Combined data suggested that overexpression of HIF-1α in HCC was not only correlated with poorer OS [HR = 1.75 (95% CI: 1.53-2.00)] and DFS [HR = 1.64 (95% CI: 1.34-2.00)] but was also positively associated with vascular invasion [OR = 1.83 (95% CI: 1.36-2.48)], tumor size [OR = 1.36 (95% CI: 1.12-1.66)], and tumor number [1.74 (95% CI: 1.34-2.25)]. In contrast, HIF-2α overexpression was not associated with the prognosis and clinicopathological features of HCC.

Conclusion: Our data provided compelling evidence of a worse prognosis of HCC in HIF-1α overexpression patients but not HIF-2α overexpression ones.

Keywords: HIF-1α; HIF-2α; hepatocellular carcinoma; meta-analysis; prognosis.

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