title: The validation of matrix metalloproteinase-9 mRNA gene expression as a predictor of outcome in patients with metastatic gastric cancer.
abstract: BACKGROUND
  The prognostic role of matrix metalloproteinase-9 (MMP-9) in metastatic gastric cancer has not been validated.
  
  
  METHODS
  We carried out a molecular analysis in 222 metastatic gastric cancer patients obtained from clinical trials. We assessed the messenger RNA (mRNA) expression of MMP-9, vascular endothelial growth factor receptor-A, and epidermal growth factor receptor in a training cohort of 130 patients and conducted an independent validation in 92 patients. Automated RNA extraction from paraffin and RT-quantitative PCR was used. Immunohistochemistry for MMP-9 and diverse immune cell infiltrates was conducted.
  
  
  RESULTS
  In the training cohort, only MMP-9 significantly correlated with patient's survival. At the cut-off with the highest predictive value, 19% of patients had MMP-9 expression above this cut-off and these showed a median survival of 3.6 months compared with 10.5 months (P=1.7e(-6)) in patients with lower expression. Corresponding 1- and 2-year survivals were 9% and 44% and 0 and 21%, respectively. The application of this cut-off to the validation cohort revealed similar distributions of overall survival according to MMP-9 expression on uni- (P<0.001) and multivariate analyses (P<0.001). No differences in survival according to MMP-9 below best cut-off were found. MMP-9 protein assessed by immunohistochemistry was not prognostic.
  
  
  CONCLUSIONS
  MMP-9 mRNA expression above a certain cut-off level is associated with dismal survival.
authors: Department of Hematology and Oncology, Institute of clinical research (IKF) at Krankenhaus Nordwest, UCT-University Cancer Center, Frankfurt am Main, Germany. albatran@aol.com
authors: S-E
authors: SE
authors: Al-Batran
authors: C
authors: C
authors: Pauligk
authors: R
authors: R
authors: Wirtz
authors: D
authors: D
authors: Werner
authors: K
authors: K
authors: Steinmetz
authors: N
authors: N
authors: Homann
authors: H
authors: H
authors: Schmalenberg
authors: R-D
authors: RD
authors: Hofheinz
authors: J T
authors: JT
authors: Hartmann
authors: A
authors: A
authors: Atmaca
authors: H-M
authors: HM
authors: Altmannsberger
authors: E
authors: E
authors: Jäger
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000201:enzymology* / Q000401:mortality / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D017326:Clinical Trials, Phase III as Topic; D000077143:Docetaxel; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D015870:Gene Expression; D006801:Humans; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D015999:Multivariate Analysis; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011379:Prognosis; D016016:Proportional Hazards Models; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D009944:Organoplatinum Compounds; D043823:Taxoids; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000077150:Oxaliplatin; D000077143:Docetaxel; D066246:ErbB Receptors; D020780:Matrix Metalloproteinase 9; D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil