Decreased Expression of the FOXO3a Gene Is Associated with Poor Prognosis in Primary Gastric Adenocarcinoma Patients

作者:Yang, Xiao-bo; Zhao, Jing-jing; Huang, Chun-yu; Wang, Qi-jing; Pan, Ke; Wang, Dan-dan; Pan, Qiu-zhong; Jiang, Shan-shan; Lv, Lin; Gao, Xiang; Chen, Huang-wei; Yao, Jia-yin; Zhi, Min*; Xia, Jian-chuan
来源:PLos One, 2013, 8(10): e78158.
DOI:10.1371/journal.pone.0078158

摘要

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.