Increased expression of MMP-9 and IL-8 are correlated with poor prognosis of Bladder Cancer.
BACKGROUND
Extracellular matrix homeostasis is strictly maintained by a coordinated balance between the expression of metalloproteinases (MMPs) and their inhibitors. The purpose of this study was to investigate whether the expression of MMP-9, MMP-2 and its specific inhibitors, are expressed in a reproducible, specific pattern and if the profiles are related to prognosis in Bladder Cancer (BC).


METHODS
MMP-9, MMP-2 and its specific inhibitors expression levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) in fresh-frozen malignant tissue collected from 40 patients with BC submitted to transurethral resection of bladder. The control group consisted of normal bladder tissue from five patients who had undergone retropubic prostatectomy to treat benign prostatic hyperplasia.


RESULTS
MMP-9 was overexpressed in 59.0 % of patients, and MMP-2, TIMP-1, TIMP-2, MMP-14, RECK and IL-8 was underexpressed in most of the patients. Regarding prognostic parameters we observed that high-grade tumors exhibited significantly higher levels of MMP-9 and IL-8 (p = 0.012, p = 0.003). Invasive tumors (pT1-pT2) had higher expression levels of MMP-9 than superficial tumors (pTa) (p = 0.026). The same was noted for IL-8 that was more expressed by invasive tumors (p = 0.015, p = 0.048). Most importantly tumor recurrence was related with higher levels of both MMP-9 (p = 0.003) and IL-8 (p = 0.005).


CONCLUSIONS
We have demonstrated that the overexpression of MMP-9 and higher expression of IL-8 are related to unfavorable prognostic factors of urothelial bladder cancer and tumor recurrence and may be useful in the follow up of the patients.
Urology Department, University of Sao Paulo Medical School, Sao Paulo, Brazil.
Sabrina Thalita
ST
Reis
Katia Ramos M
KR
Leite
Luís Felipe
LF
Piovesan
José
J
Pontes-Junior
Nayara Izabel
NI
Viana
Daniel Kanda
DK
Abe
Alexandre
A
Crippa
Caio Martins
CM
Moura
Sanarelly Pires
SP
Adonias
Miguel
M
Srougi
Marcos Francisco
MF
Dall'Oglio
D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002295:Carcinoma, Transitional Cell; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D053511:Matrix Metalloproteinase 14 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000235:genetics*
D014408:Biomarkers, Tumor; C508606:CXCL8 protein, human; D058851:GPI-Linked Proteins; D016209:Interleukin-8; C115460:RECK protein, human; D019714:Tissue Inhibitor of Metalloproteinases; D020780:Matrix Metalloproteinase 9; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14