FABP4 suppresses proliferation and invasion of hepatocellular carcinoma cells and predicts a poor prognosis for hepatocellular carcinoma

Cancer Med. 2018 Jun;7(6):2629-2640. doi: 10.1002/cam4.1511. Epub 2018 May 7.

Abstract

Adipocyte fatty acid-binding protein (FABP4) is abundant in macrophage and adipocyte. It is known to be involved in lipid metabolism. The role of FABP4 has been reported in various cancers, such as non-small cell lung cancer, breast cancer, ovarian cancer, and prostatic cancer. However, its role remains unclear in hepatocellular carcinoma (HCC). In our study, we investigated the expression of FABP4 at both mRNA and protein levels, and by examining 175 cases of patients with cancer of the liver tissue microarray, the significance between the expression of FABP4 and clinical characteristics had been discussed. We found that FABP4 was lowly expressed in HCC tissues compared to the corresponding tissue adjacent, and the expression of FABP4 was significantly associated with the tumor size, PVTT, recurrence-free survival and overall survival. Moreover, multivariate Cox regression analysis indicated that the expression of FABP4, Alb, AFP, HBsAg, and PVTT were independent risk factors for overall survival, and the expression of FABP4, AFP, GGT, tumor size, and encapsulation were independent risk factors for HCC recurrence. In addition, we revealed that FABP4 suppressed HCC cell proliferation and invasion in vitro. Moreover, overexpression of FABP4 led to inhibit tumor growth and decreased tumor volume in vivo. These phenotypes were associated with altered expression of Snail and p-STAT3. Our studies thus suggest that FABP4 could be a potential target for HCC chemotherapy.

Keywords: Fatty acid-binding protein 4; hepatocellular carcinoma; poor prognosis; proliferation and invasion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Biomarkers, Tumor*
  • Carcinoma, Hepatocellular / diagnosis
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / mortality*
  • Carcinoma, Hepatocellular / therapy
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Disease Models, Animal
  • Fatty Acid-Binding Proteins / genetics*
  • Fatty Acid-Binding Proteins / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Heterografts
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / mortality*
  • Liver Neoplasms / therapy
  • Male
  • Mice
  • Middle Aged
  • Prognosis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • Biomarkers, Tumor
  • FABP4 protein, human
  • Fatty Acid-Binding Proteins
  • RNA, Messenger