Loss of Protein Tyrosine Phosphatase Receptor J Expression Predicts an Aggressive Clinical Course in Patients with Esophageal Squamous Cell Carcinoma

Pathol Oncol Res. 2016 Jul;22(3):541-7. doi: 10.1007/s12253-015-0036-3. Epub 2015 Dec 23.

Abstract

Protein Tyrosine Phosphatase Receptor J (PTPRJ) has been reported to be a tumor suppressor in various human cancers. The aim of this study was to investigate the clinical significance of PTPRJ in ESCC patients and its effects on biological behaviors of ESCC cells. PTPRJ expression, at mRNA and protein levels, were respectively detected by quantitative real-time PCR, western blot and immunohistochemistry, based on 106 newly diagnosed ESCC patients. The associations between PTPRJ expression and clinicopathological characteristics of ESCC patients were statistically analyzed. Then, the effects of PTPRJ in migration and invasion were determined by wound healing and transwell assays based on ESCC cell line transfected with siRNA or expression vector of PTPRJ. Expression of PTPRJ at mRNA and protein levels were both significantly lower in ESCC tissues than those in normal esophageal mucosa. Immunohistochemistry showed that PTPRJ protein was localized in the cytoplasm of cancer cells in ESCC tissues. In addition, PTPRJ downregulation was found to be closely correlated with advanced tumor stage (P = 0.01) and poor differentiation (P = 0.03). Moreover, knockdown of PTPRJ in KYSE510 cells could significantly promote cell migration and invasion (both P < 0.05), which were reversed by the restoration of PTPRJ expression in vitro (both P < 0.05). Our data offer the convincing evidence that loss of PTPRJ expression may predict an aggressive clinical course in ESCC patients. PTPRJ may function as a tumor suppressor and play an important role in the regulation of ESCC cell motility, suggesting its potentials as a therapeutic agent for human ESCC.

Keywords: Esophageal squamous cell carcinoma; Invasion; Migration; Progression; Protein tyrosine phosphatase receptor J.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Down-Regulation / genetics
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / pathology*
  • Esophageal Squamous Cell Carcinoma
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Immunohistochemistry / methods
  • Kaplan-Meier Estimate
  • Lymphatic Metastasis / genetics
  • Lymphatic Metastasis / pathology
  • Male
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics
  • Receptor-Like Protein Tyrosine Phosphatases, Class 3 / genetics

Substances

  • Biomarkers, Tumor
  • RNA, Messenger
  • RNA, Small Interfering
  • PTPRJ protein, human
  • Receptor-Like Protein Tyrosine Phosphatases, Class 3