Decreased expression of the FOXO3a gene is associated with poor prognosis in primary gastric adenocarcinoma patients

PLoS One. 2013 Oct 23;8(10):e78158. doi: 10.1371/journal.pone.0078158. eCollection 2013.

Abstract

Background: FOXO3a, a member of the forkhead class 'O' (FOXO) transcription factor family, controls a wide spectrum of biological processes, such as DNA damage repair, apoptosis, and cell cycle regulation. FOXO3a has been shown to be a tumor suppressor in various cancers. This study investigated the expression of FOXO3a in primary gastric adenocarcinomas and its prognostic value for primary gastric adenocarcinoma patients.

Methods: Real-time quantitative RT-PCR (qRT-PCR), western blotting, and immunohistochemical staining were used to detect FOXO3a expression in primary gastric cancerous surgical specimens and adjacent non-tumorous tissues.

Results: Our data showed that the expression of FOXO3a mRNA (p = 0.03) and protein (p = 0.019) was lower in cancerous tissues compared with their adjacent non-tumorous tissues. In addition, the chi-square test revealed that low FOXO3a expression was significantly correlated with larger tumor size (p = 0.007), poor histopathological classification (p = 0.029), depth of invasion (p = 0.049), local lymph node metastasis (p = 0.013), distant metastasis (p = 0.013) and AJCC staging (p<0.001). Kaplan-Meier survival analysis demonstrated that low expression of FOXO3a was significantly correlated with a poor prognosis for gastric cancer patients (p<0.001). The multivariate analysis showed that FOXO3a expression was an independent prognostic factor of the overall survival rate of patients with primary gastric adenocarcinoma.

Conclusion: Our study suggested that decreased FOXO3a expression may play an important role in the progression of gastric cancer. FOXO3a could be a valuable prognostic marker as well as a potential molecular therapy target for gastric cancer patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / diagnosis
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Blotting, Western
  • Forkhead Box Protein O3
  • Forkhead Transcription Factors / metabolism*
  • Gene Expression Regulation, Neoplastic / physiology*
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Multivariate Analysis
  • Neoplasm Metastasis / diagnosis*
  • Prognosis
  • Real-Time Polymerase Chain Reaction
  • Stomach Neoplasms / diagnosis
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology

Substances

  • FOXO3 protein, human
  • Forkhead Box Protein O3
  • Forkhead Transcription Factors

Grants and funding

This work was supported by the National Natural Science Foundation of China (u0772002, 30700985, 30973398) and Guangdong Natural Science Foundation (925100890). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.