Prognostic Value of Phosphotyrosine Phosphatases in Hepatocellular Carcinoma

Cell Physiol Biochem. 2018;46(6):2335-2346. doi: 10.1159/000489625. Epub 2018 May 4.

Abstract

Background/aims: During the occurrence and progression of hepatocellular carcinoma (HCC), phosphotyrosine phosphatases (PTPs) are usually described as tumor suppressors or proto-oncogenes, and to some degree are correlated with the prognosis of HCC.

Methods: A total of 321 patients from the Cancer Genome Atlas (TCGA) database and 180 patients from our validated cohort with hepatocellular carcinoma were recruited in this study. Kaplan-Meier, univariate and multivariate Cox proportional hazards model were used to evaluate the risk factors for survival. Quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC) were applied to detect the expression levels of PTP genes.

Results: After screening the data of TCGA, we identified five PTPs as HCC overall survival related PTP genes, among which only three (PTPN12, PTPRN, PTPN18) exhibited differential expression levels in our 180 paired HCC and adjacent tissues (P< 0.001). Further analysis revealed that expression of PTPN18 was positively, but PTPRN was negatively associated with prognosis of HCC both in TCGA cohort and our own cohort. As to PTPN12, results turned out to be opposite according to HBV status. In detail, higher expression of PTPN12 was associated with better outcome in HBV group but worse prognosis in Non-HBV group.

Conclusion: Our results suggested that PTPN12, PTPRN and PTPN18 were independent prognostic factors in HCC.

Keywords: Cancer specific survival; Hepatocellular carcinoma; Phosphotyrosine phosphatase; TCGA.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Hepatocellular / diagnosis
  • Carcinoma, Hepatocellular / genetics*
  • Cohort Studies
  • Female
  • Gene Expression Regulation
  • Humans
  • Kaplan-Meier Estimate
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / genetics*
  • Male
  • Middle Aged
  • Prognosis
  • Protein Tyrosine Phosphatase, Non-Receptor Type 12 / analysis
  • Protein Tyrosine Phosphatase, Non-Receptor Type 12 / genetics*
  • Protein Tyrosine Phosphatases, Non-Receptor / analysis
  • Protein Tyrosine Phosphatases, Non-Receptor / genetics*
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8 / analysis
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8 / genetics*

Substances

  • PTPN12 protein, human
  • PTPN18 protein, human
  • PTPRN protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 12
  • Protein Tyrosine Phosphatases, Non-Receptor
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8