Platelet-derived growth factor receptor α in hepatocellular carcinoma is a prognostic marker independent of underlying liver cirrhosis

Oncotarget. 2017 Jun 13;8(24):39534-39546. doi: 10.18632/oncotarget.17134.

Abstract

Background and aims: Platelet-derived growth factor receptor alpha (PDGFRα) is suggested as a prognosis marker for hepatocellular carcinoma (HCC). Since PDGFRα is also known as a marker for activated hepatic stellate cells (HSCs), this study aimed to investigate whether PDGFRα expression in HCC was dependent on the background liver fibrous condition.

Results: Strong PDGFRα expression in the tumor lesions was associated with decreased survival after curative HCC resection. Expression of PDGFRα in the tumor correlated with increased collagen α1(I), lecithin retinol acyltransferase, and smooth muscle α-actin suggesting increased HSCs in tumor sites. The expression of PDGFRα in the tumor sites was associated neither with underlying liver fibrosis/cirrhosis nor with the expression of PDGFRα in adjacent non-tumor sites of the liver.

Materials and methods: Patients with HCC who underwent liver resection as curative treatment were included in this study. Using liver samples of 95 patients, tissue microarray was constructed and immunohistochemical study of PDGFRα was conducted in both tumor and non-tumor sites. PDGFRα expression in tumor and matching non-tumor sites was compared. Freshly frozen liver tissue specimens of 16 HCC patients were used for gene expression analysis of PDGFRα and fibrosis related genes.

Conclusions: Our results suggest that PDGFRα overexpression in HCC is a prognostic marker independent of adjacent non-tumor site liver fibrosis status.

Keywords: hepatic stellate cell; hepatocellular carcinoma; liver cirrhosis; liver fibrosis; platelet-derived growth factor receptor α.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / mortality*
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / therapy
  • Female
  • Follow-Up Studies
  • Humans
  • Immunohistochemistry
  • Liver Cirrhosis / pathology*
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / mortality*
  • Liver Neoplasms / pathology
  • Liver Neoplasms / therapy
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Prognosis
  • Receptor, Platelet-Derived Growth Factor alpha / genetics
  • Receptor, Platelet-Derived Growth Factor alpha / metabolism*
  • Survival Analysis

Substances

  • Biomarkers, Tumor
  • Receptor, Platelet-Derived Growth Factor alpha