Down-regulation of C/EBP homologous protein (CHOP) expression in gastric cardia adenocarcinoma: Their relationship with clinicopathological parameters and prognostic significance

Clin Res Hepatol Gastroenterol. 2015 Jun;39(3):391-8. doi: 10.1016/j.clinre.2014.11.010. Epub 2015 Jan 9.

Abstract

Objective: C/EBP homologous protein (CHOP) is a multi-functional protein involved in the apoptosis pathway of endoplasmic reticulum stress (ERS) and is related to cancer progression. The purpose of this study was to assess CHOP expression as a prognostic biomarker in gastric cardia adenocarcinoma (GCA).

Methods: The levels of CHOP mRNA and protein in GCA and matched adjacent non-cancerous tissues were evaluated by quantitative real-time-polymerase chain reaction (qRT-PCR) and western blot. Furthermore, the CHOP protein expression and localization were examined by immunohistochemistry in GCA and corresponding adjacent non-cancerous tissues, gastritis and normal cardiac tissues. The association of CHOP expression with clinical pathological parameters and prognosis of GCA patients was statistically analyzed.

Results: Compared with adjacent non-cancerous tissues, the CHOP was down-regulated at mRNA and protein levels in GCA (P<0.01). In addition, immunohistochemistry analysis showed that CHOP positivity was lower in GCA than that in paired adjacent non-cancerous tissues, gastritis and normal tissues (P<0.01). CHOP expression rate gradually decreased with an increase in clinical stage, tumor differentiation and lymph node metastasis of GCA (P<0.05). Kaplan-Meier survival analysis revealed that low expression of CHOP correlated with poor prognosis of GCA patients. Moreover, univariate and multivariate analyses showed that CHOP was an independent prognostic marker for overall survival of GCA patients.

Conclusions: Our results suggest that low CHOP expression predicts poor prognosis of GCA patients, and CHOP may be potentially a prognostic biomarker for GCA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology*
  • Down-Regulation*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology*
  • Survival Rate
  • Transcription Factor CHOP / biosynthesis*

Substances

  • Transcription Factor CHOP