title: MMP, VEGF and TIMP as prognostic factors in recurring bladder cancer.
abstract: OBJECTIVE
  To investigate the clinical correlates and prognostic utility of MMP, VEGF and TIMP genes expression in bladder cancer (BCa) recurrence.
  
  
  METHODS
  Expression of MMP1, MMP2, MMP9, VEGFA and TIMP1, TIMP3 was analyzed by qRT-PCR using SYBR Green in peripheral blood leukocytes (PBLs) of BCa patients at two time points (diagnosis (n=40), and first recurrence (n=40)) and an age-matched group of healthy controls (n=100). Plasma concentrations of MMP1 (pro- and active forms) were measured using ELISA in BCa patients.
  
  
  RESULTS
  The expression of MMP1 mRNA was significantly lower in BCa patients with first recurrence compared to control (p=0.019). Expression of other genes did not differ significantly between the groups. MMP9 gene expression was associated with differentiation grade (p=0.043), with the highest expression in poorly differentiated tumors (G3) and was higher in smokers than in non-smokers (p=0.039) in BCa patients at diagnosis. The results at two time points showed that MMP9 and VEGFA genes expression was increased in patients with moderately differentiated BCa (p=0.029), and advanced pathologic stage (p=0.048), respectively. Moreover, gene expression of TIMP1 was increased for G3 (p=0.043), and was decreased for early recurrence (p=0.003).
  
  
  CONCLUSIONS
  Our study suggests that the expression of MMP9 in PBLs of BCa patients at diagnosis is associated with the differentiation grade of the BCa, and smoking status. Genes expression of MMP9, VEGFA and TIMP1 in PBLs may play a pivotal role in regulation of progression of BCa. Additionally, TIMP1 gene expression may be important factor for early recurrence of BCa.
authors.affiliation: Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, Lodz, Poland. Electronic address: edytaw@imp.lodz.pl.
authors.forename: E
authors.initials: E
authors.lastname: Wieczorek
authors.affiliation: 1st Department of Urology, Medical University of Lodz, Poland.
authors.forename: Z
authors.initials: Z
authors.lastname: Jablonowski
authors.affiliation: Department of Pediatrics, Oncology, Hematology and Diabetology, Medical University of Lodz, Poland.
authors.forename: B
authors.initials: B
authors.lastname: Tomasik
authors.affiliation: 1st Department of Urology, Medical University of Lodz, Poland.
authors.forename: T
authors.initials: T
authors.lastname: Konecki
authors.affiliation: Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, Lodz, Poland.
authors.forename: E
authors.initials: E
authors.lastname: Jablonska
authors.affiliation: Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, Lodz, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Gromadzinska
authors.affiliation: Department of Pediatrics, Oncology, Hematology and Diabetology, Medical University of Lodz, Poland.
authors.forename: W
authors.initials: W
authors.lastname: Fendler
authors.affiliation: 1st Department of Urology, Medical University of Lodz, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Sosnowski
authors.affiliation: Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, Lodz, Poland.
authors.forename: W
authors.initials: W
authors.lastname: Wasowicz
authors.affiliation: Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, Lodz, Poland.
authors.forename: E
authors.initials: E
authors.lastname: Reszka
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000097:blood / Q000235:genetics; D020778:Matrix Metalloproteinase 2 / Q000097:blood / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000097:blood / Q000235:genetics*; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D012307:Risk Factors; D012907:Smoking / Q000503:physiopathology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood / Q000235:genetics*; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000097:blood / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C560822:TIMP1 protein, human; C088390:TIMP3 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019717:Tissue Inhibitor of Metalloproteinase-3; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1
keywords: Bladder cancer recurrence; Gene expression; MMP; TIMP; VEGF