Reduced expression of transcription factor AP-2α is associated with gastric adenocarcinoma prognosis

PLoS One. 2011;6(9):e24897. doi: 10.1371/journal.pone.0024897. Epub 2011 Sep 26.

Abstract

Background: This study aims to investigate the expression and prognostic significance of activator protein 2α (AP-2α) in gastric adenocarcinoma.

Methodology/principal findings: AP-2α expression was analyzed using real-time quantitative PCR (RT-qPCR), western blotting, and immunohistochemical staining methods on tissue samples from a consecutive series of 481 gastric adenocarcinoma patients who underwent resections between 2003 and 2006. The relationship between AP-2α expression, clinicopathological factors, and patient survival was investigated. RT- qPCR results showed that the expression of AP-2α mRNA was reduced in tumor tissue samples, compared with expression in matched adjacent non-tumor tissue samples (P = 0.009); this finding was confirmed by western blotting analysis (P = 0.012). Immunohistochemical staining data indicated that AP-2α expression was significantly decreased in 196 of 481 (40.7%) gastric adenocarcinoma cases; reduced AP-2α expression was also observed in patients with poorly differentiated tumors (P = 0.001) and total gastric carcinomas (P = 0.002), as well as in patients who underwent palliative tumor resection (P = 0.004). Additionally, reduced expression of AP-2α was more commonly observed in tumors that were staged as T4a/b (P = 0.018), N3 (P = 0.006), and M1 (P = 0.008). Kaplan-Meier survival curves revealed that reduced expression of AP-2α was associated with poor prognosis in gastric adenocarcinoma patients (P<0.001). Multivariate Cox analysis identified AP-2α expression as an independent prognostic factor for overall survival (HR = 1.512, 95% CI = 1.127-2.029, P = 0.006).

Conclusions/significance: Our data suggest that AP-2α plays an important role in tumor progression and that reduced AP-2α expression independently predicts an unfavorable prognosis in gastric adenocarcinoma patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Blotting, Western
  • Down-Regulation
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Prognosis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology
  • Transcription Factor AP-2 / genetics*
  • Transcription Factor AP-2 / metabolism
  • Young Adult

Substances

  • Transcription Factor AP-2