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

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.

• Authors: Xiao-bo Yang, Jing-jing Zhao, Chun-yu Huang, Qi-jing Wang, Ke Pan, Dan-dan Wang, Qiu-zhong Pan, Shan-shan Jiang, Lin Lv, Xiang Gao, Huang-wei Chen, Jia-yin Yao, Min Zhi, Jian-chuan Xia
• Journal: PloS one (PLoS One) Vol. 8 Issue 10 Pg. e78158 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 24194912 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• Adenocarcinoma (diagnosis, metabolism, 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, metabolism, pathology)