title: Aberrant upregulation of 14-3-3ơ expression serves as an inferior prognostic biomarker for gastric cancer.
abstract: BACKGROUND
  14-3-3ơ is an intracellular, phosphoserine binding protein and proposed to be involved in tumorigenesis. However, the expression dynamics of 14-3-3ơ and its clinicopathological/prognostic significance in human tumors are still controversial.
  
  
  METHODS
  The method of immunohistochemistry (IHC) and Western blot were utilized to examine the protein expression of 14-3-3ơ in gastric cancer and paired normal adjacent gastric mucosal tissues. Receive operating characteristic (ROC) curve analysis was employed to determine a cutoff score for 14-3-3ơ expression in a training set (n = 66). For validation, the ROC-derived cutoff score was subjected to analysis of the association of 14-3-3ơ expression with patient outcome and clinical characteristics in a testing set (n = 86) and overall patients (n = 152).
  
  
  RESULTS
  The expression frequency and expression levels of 14-3-3ơ were significantly higher in gastric cancer than in normal gastric mucosal tissues. Correlation analysis demonstrated that high expression of 14-3-3ơ in gastric cancer was significantly correlated with clinical stage and tumor invasion. Furthermore, in the testing set and overall patients, Kaplan-Meier analysis showed that elevated 14-3-3ơ expression predicted poorer overall survival (OS) and progression-free survival (PFS). Importantly, high 14-3-3ơ expression was also associated with shortened survival time in stage III and stage IV gastric cancer patients. Multivariate analyses revealed that 14-3-3ơ expression was an independent prognostic parameter in gastric cancer.
  
  
  CONCLUSIONS
  These findings provide evidence that high expression of 14-3-3ơ may be important in the tumor progression and servers as an independent molecular marker for poor prognosis of gastric cancer. Thus, overexpression of 14-3-3ơ identifies patients at high risk and is a novel therapeutic molecular target for this tumor.
authors.affiliation: Department of Hematology, the Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China. shaock2001@yahoo.com
authors.forename: Wei-hua
authors.initials: WH
authors.lastname: Zhou
authors.forename: Fang
authors.initials: F
authors.lastname: Tang
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.forename: Xing
authors.initials: X
authors.lastname: Wu
authors.forename: Zhi-ying
authors.initials: ZY
authors.lastname: Feng
authors.forename: Hai-gang
authors.initials: HG
authors.lastname: Li
authors.forename: Dong-jun
authors.initials: DJ
authors.lastname: Lin
authors.forename: Chun-kui
authors.initials: CK
authors.lastname: Shao
authors.forename: Quentin
authors.initials: Q
authors.lastname: Liu
mesh_terms: D048948:14-3-3 Proteins / Q000096:biosynthesis* / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D015153:Blotting, Western; D018450:Disease Progression; D018572:Disease-Free Survival; D005092:Exonucleases / Q000096:biosynthesis* / Q000235:genetics; D005095:Exoribonucleases; D005260:Female; D005500:Follow-Up Studies; D005753:Gastric Mucosa / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012372:ROC Curve; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism*; D046888:Tissue Array Analysis; D015854:Up-Regulation
chemical_list: D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D005092:Exonucleases; D005095:Exoribonucleases; C413442:SFN protein, human