Poor prognosis of gastric adenocarcinoma with decreased expression of AHRR

PLoS One. 2012;7(8):e43555. doi: 10.1371/journal.pone.0043555. Epub 2012 Aug 27.

Abstract

Background: The aryl hydrocarbon receptor (AHR) repressor (AHRR), a member of growing superfamily, is a basic-helix-loop-helix/Per-AHR nuclear translocator (ARNT)-Sim (bHLH-PAS) protein. Recently, AHRR has been proposed to function as a putative new tumor suppressor gene based on some relevant studies in multiple types of human cancers. This current study aims to investigate AHHR expression and its prognostic significance in primary gastric adenocarcinoma.

Methodology/principal findings: The expression level of AHRR was analyzed using real-time quantitative PCR (RT-qPCR), western blotting, and immunohistochemical staining. It was clearly showed that the expression status of AHRR was reduced in tumor tissue samples compared with that in matched adjacent non-tumor tissue samples by RT-qPCR (P = 0.0423) and western blotting analysis (P = 0.004). Moreover, data revealed that AHRR without exon 8 (the active isoform) was the predominant form either in tumor tissues (66.7%, 8/12) or in matched adjacent non-tumor tissues (100.0%, 12/12), and the mRNA level of this isoform was significantly reduced in tumor tissues (P = 0.006). Immunohistochemistry analysis indicated that AHRR expression was significantly decreased in 175 of 410 (42.7%) gastric adenocarcinoma cases. Kaplan-Meier survival curves and Multivariate Cox analysis revealed that decreased expression of AHRR was significantly associated with poor prognosis in gastric adenocarcinoma patients.

Conclusions/significance: Our data suggests that, in primary gastric adenocarcinoma, AHRR may play as a suppressor gene and its expression status has the potential to be an independent prognostic factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Adenocarcinoma / diagnosis*
  • Basic Helix-Loop-Helix Transcription Factors / biosynthesis*
  • Exons
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry / methods
  • Multivariate Analysis
  • Polymerase Chain Reaction
  • Prognosis
  • RNA, Messenger / metabolism
  • Repressor Proteins / biosynthesis*
  • Retrospective Studies
  • Stomach Neoplasms / diagnosis*

Substances

  • AHRR protein, human
  • Basic Helix-Loop-Helix Transcription Factors
  • RNA, Messenger
  • Repressor Proteins

Grants and funding

This work was supported by the Guangdong Province Science and Technology Project (2009B080701006). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.