title: The influence of transforming growth factor-α, cyclooxygenase-2, matrix metalloproteinase (MMP)-7, MMP-9 and CXCR4 proteins involved in epithelial-mesenchymal transition on overall survival of patients with gastric cancer.
abstract: OBJECTIVE
  Determination of prognostic parameters that are predictive of survival of gastric cancer (GC) may allow better identification of patients who could benefit from current chemotherapy regimens. To assess the correlation between tumour progression and epithelial-mesenchymal transition (EMT), we assayed the expression levels of selected molecules involved in EMT [CD44, transforming growth factor (TGF)-α, cyclooxygenase-2 (COX-2), matrix metalloproteinase (MMP)-7, MMP-9 and C-X-C chemokine receptor (CXCR4)], and correlated these with overall patient survival (OS) and disease stage.
  
  
  RESULTS
  Medical records and pathological biopsy results of 137 patients with GC were evaluated retrospectively. Spearman's correlation analysis showed that expression of CXCR4 was correlated significantly with the expression of all other proteins studied. In contrast, COX-2 expression correlated significantly with the expression of only MMP-7 (P = 0.011), MMP-9 (P = 0.015) and CXCR4 (P = 0.013). We observed significant negative correlations between OS and the expression of TGF-α (P = 0.017), COX-2 (P < 0.001), CXCR4 (P = 0.010), MMP-7 (P = 0.020) and MMP-9 (P = 0.015). On multivariate analysis, only COX-2 was an independent prognostic factor for OS [hazard ratio (HR) = 3.34; 95% confidence interval (CI): 1.43-9.75; P = 0.002).
  
  
  CONCLUSIONS
  COX-2, TGF-α, MMP-7, MMP-9 and CXCR4 are associated with poor OS in gastric cancer.
authors.affiliation: Fundação Antônio Prudente, Hospital do Câncer A. C. Camargo, São Paulo, Brazil. mffanelli@gmail.com
authors.forename: Marcello Ferretti
authors.initials: MF
authors.lastname: Fanelli
authors.forename: Ludmilla T Domingos
authors.initials: LT
authors.lastname: Chinen
authors.forename: Maria Dirlei
authors.initials: MD
authors.lastname: Begnami
authors.forename: Wilson Luis
authors.initials: WL
authors.lastname: Costa
authors.forename: José Humberto T
authors.initials: JH
authors.lastname: Fregnami
authors.forename: Fernando A
authors.initials: FA
authors.lastname: Soares
authors.forename: André Luis
authors.initials: AL
authors.lastname: Montagnini
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D019718:Receptors, CXCR4 / Q000378:metabolism*; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology*; D046888:Tissue Array Analysis; D016211:Transforming Growth Factor alpha / Q000378:metabolism*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C112697:CD44v6 antigen; C527276:CXCR4 protein, human; D018960:Hyaluronan Receptors; D019718:Receptors, CXCR4; D016211:Transforming Growth Factor alpha; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7; D020780:Matrix Metalloproteinase 9