Hypoxia inducible factor 1α in hepatocellular carcinoma with cirrhosis: Association with prognosis

Pathol Res Pract. 2018 Dec;214(12):1987-1992. doi: 10.1016/j.prp.2018.09.007. Epub 2018 Sep 13.

Abstract

Background: Hypoxia inducible factor 1α (HIF-1α) is a protein related with carcinogenesis and metastasis in many tumors. However, little is known about the prognostic value of HIF-1α in hepatocellular carcinoma (HCC) patients with cirrhosis.

Methods: Clinical-pathological information and follow-up data were collected from HCC (n = 419) and chronic hepatitis (n = 49) patients. HIF-1α expression was scored based on the percentage of immunohistochemical staining. Correlations between HIF-1α expression and clinical features were evaluated by Chi-square test. And survival analysis was performed by multivariate Cox regression analysis.

Results: In cirrhosis patients, the frequency of HIF-1α positive expression in HCC was higher than in chronic hepatitis (P = 0.002). HIF-1α positive expression was significantly associated with vascular invasion (P = 0.002), TNM stage (P = 0.005), HBV infection (P = 0.005), tumor size (P = 0.025) and portal vein tumor thrombus (P = 0.001) in HCC with liver cirrhosis. While, in cirrhosis-free patients, HIF-1α positive expression had a significant correlation with vascular invasion (P = 0.039) and AFP value (P = 0.001) in. HIF-1α "positive" had decreased overall survival compared to HIF-1α "negative" patients and this was an independent adverse prognostic factor (multivariable analysis P = 0.001) for HCC patients with cirrhosis, but not for cirrhosis-free patients.

Conclusions: Our results suggested that HIF-1α served as a poor prognostic factor for HCC patients with cirrhosis.

Keywords: Cirrhosis; Hepatocellular carcinoma; Hypoxia inducible factor 1α; Prognosis.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Hepatocellular / complications
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Liver / metabolism*
  • Liver Cirrhosis / complications
  • Liver Cirrhosis / metabolism*
  • Liver Cirrhosis / pathology
  • Liver Neoplasms / complications
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Prognosis

Substances

  • Biomarkers, Tumor
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit