title: 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.
  
  
  CONCLUSIONS
  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.affiliation: State Key Laboratory of Oncology in Southern China and Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China ; Department of Gastroenterology, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, P.R. China.
authors.forename: Xiao-bo
authors.initials: XB
authors.lastname: Yang
authors.forename: Jing-jing
authors.initials: JJ
authors.lastname: Zhao
authors.forename: Chun-yu
authors.initials: CY
authors.lastname: Huang
authors.forename: Qi-jing
authors.initials: QJ
authors.lastname: Wang
authors.forename: Ke
authors.initials: K
authors.lastname: Pan
authors.forename: Dan-dan
authors.initials: DD
authors.lastname: Wang
authors.forename: Qiu-zhong
authors.initials: QZ
authors.lastname: Pan
authors.forename: Shan-shan
authors.initials: SS
authors.lastname: Jiang
authors.forename: Lin
authors.initials: L
authors.lastname: Lv
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.forename: Huang-wei
authors.initials: HW
authors.lastname: Chen
authors.forename: Jia-yin
authors.initials: JY
authors.lastname: Yao
authors.forename: Min
authors.initials: M
authors.lastname: Zhi
authors.forename: Jian-chuan
authors.initials: JC
authors.lastname: Xia
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis / Q000175:diagnosis*; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology
chemical_list: C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors