E Wieczorek1, Z Jablonowski2, B Tomasik3, T Konecki2, E Jablonska4, J Gromadzinska4, W Fendler3, M Sosnowski2, W Wasowicz4, E Reszka4. 1. Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, Lodz, Poland. Electronic address: edytaw@imp.lodz.pl. 2. 1st Department of Urology, Medical University of Lodz, Poland. 3. Department of Pediatrics, Oncology, Hematology and Diabetology, Medical University of Lodz, Poland. 4. Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, Lodz, Poland.
Abstract
OBJECTIVES: 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.
OBJECTIVES: 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: William H Hoffman; Cornelia D Cudrici; Dallas Boodhoo; Alexandru Tatomir; Violeta Rus; Horea Rus Journal: Exp Mol Pathol Date: 2019-04-13 Impact factor: 3.362
Authors: Anne Monette; Antigoni Morou; Nadia A Al-Banna; Louise Rousseau; Jean-Baptiste Lattouf; Sara Rahmati; Tomas Tokar; Jean-Pierre Routy; Jean-François Cailhier; Daniel E Kaufmann; Igor Jurisica; Réjean Lapointe Journal: J Clin Invest Date: 2019-03-26 Impact factor: 14.808