title: TNK2 gene amplification is a novel predictor of a poor prognosis in patients with gastric cancer.
abstract: OBJECTIVE
  We previously examined the amplification status of 10 kinase genes (PIK3CA, EPHB3, TNK2, PTK7, EGFR, MET, ERBB2, HCK, SRC, and AURKA) in gastric cancer (GC). This study aimed to determine the prognostic significance of these gene amplifications in GC.
  
  
  METHODS
  A survival analysis was performed for GC patients. Since TNK2 amplification was identified as a prognostic marker in the analysis, we also examined the functional effect of TNK2 overexpression on gastric cells.
  
  
  RESULTS
  A Kaplan-Meier analysis showed that the prognosis of patients with GC exhibiting TNK2 or AURKA amplification was significantly poorer than the prognosis of patients with GC without TNK2 or AURKA amplification. A further multivariate analysis revealed that TNK2 amplification was an independent predictor of a poor survival outcome among patients with GC (hazard ratio, 3.668; 95% confidence interval, 1.513-7.968; P = 0.0056). TNK2-overexpressing GC cells showed an increase in cell migration and non-anchored cell growth. Finally, microarray and pathway analyses revealed the aberrant regulation of some cancer-related pathways in TNK2-overexpressing GC cells.
  
  
  CONCLUSIONS
  These results suggested that TNK2 amplification is an independent predictor of a poor prognosis in patients with GC and leads to an increase in the malignant potential of GC cells.
authors.affiliation: Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Shinmura
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Kiyose
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Nagura
authors.forename: Hisaki
authors.initials: H
authors.lastname: Igarashi
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Inoue
authors.forename: Satoki
authors.initials: S
authors.lastname: Nakamura
authors.forename: Matsuyoshi
authors.initials: M
authors.lastname: Maeda
authors.forename: Megumi
authors.initials: M
authors.lastname: Baba
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Konno
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Sugimura
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics*; D015153:Blotting, Western; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005784:Gene Amplification; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000032:analysis* / Q000235:genetics*; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D046888:Tissue Array Analysis; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D011505:Protein-Tyrosine Kinases; C403262:TNK2 protein, human
keywords: TNK2; gastric cancer; gene amplification; prognostic marker; survival analysis