Increased expression of MMP-9 and IL-8 are correlated with poor prognosis of Bladder Cancer

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Citações na Scopus
91
Tipo de produção
article
Data de publicação
2012
Título da Revista
ISSN da Revista
Título do Volume
Editora
BIOMED CENTRAL LTD
Citação
BMC UROLOGY, v.12, article ID 18, 5p, 2012
Projetos de Pesquisa
Unidades Organizacionais
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Resumo
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). Conclusion: 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.
Palavras-chave
Bladder cancer, Matrix metalloproteinase, Prognosis, Diagnosis, Gene expression
Referências
  1. Borden LS, 2005, CURR OPIN ONCOL, V17, P275, DOI 10.1097/01.cco.0000156985.47984.9e
  2. Chang CK, 2008, J CELL MOL MED, V12, P12
  3. Chang HC, 2004, CELL SIGNAL, V16, P675, DOI 10.1016/j.cellsig.2003.11.001
  4. Cho NH, 2003, EUR UROL, V44, P560, DOI 10.1016/S0302-2838(03)00362-2
  5. Cox G, 2000, LUNG CANCER-J IASLC, V27, P81, DOI 10.1016/S0169-5002(99)00096-3
  6. Eissa S, 2007, EUR UROL, V52, P1388, DOI 10.1016/j.eururo.2007.04.006
  7. Henriet P, 1999, APMIS, V107, P111
  8. Heppner KJ, 1996, AM J PATHOL, V149, P273
  9. Hsu MC, 2006, J BIOL CHEM, V281, P4718, DOI 10.1074/jbc.M510937200
  10. Jebar AH, 2005, ONCOGENE, V24, P5218, DOI 10.1038/sj.onc.1208705
  11. Jemal A, 2011, CA-CANCER J CLIN, V61, P69, DOI 10.3322/caac.20107
  12. Kodate M, 1997, PATHOL INT, V47, P461, DOI 10.1111/j.1440-1827.1997.tb04525.x
  13. Liabakk NB, 1996, CANCER RES, V56, P190
  14. Luca M, 1997, AM J PATHOL, V151, P1105
  15. Mian BM, 2003, CLIN CANCER RES, V9, P3167
  16. Nastase A, 2011, CHIRURGIA-BUCHAREST, V106, P177
  17. Nawrocki B, 1997, INT J CANCER, V72, P556, DOI 10.1002/(SICI)1097-0215(19970807)72:4<556::AID-IJC2>3.0.CO;2-P
  18. Oh J, 2001, CELL, V107, P789, DOI 10.1016/S0092-8674(01)00597-9
  19. Sasahara RM, 1999, BIOCHEM BIOPH RES CO, V264, P668, DOI 10.1006/bbrc.1999.1552
  20. Takahashi C, 1998, P NATL ACAD SCI USA, V95, P13221, DOI 10.1073/pnas.95.22.13221
  21. Takeuchi T, 2004, CLIN CANCER RES, V10, P5572, DOI 10.1158/1078-0432.CCR-03-0656
  22. Toi M, 1998, BREAST CANCER RES TR, V52, P113, DOI 10.1023/A:1006167202856
  23. Wallard MJ, 2006, BRIT J CANCER, V94, P569, DOI 10.1038/sj.bjc.6602931
  24. Yuan JP, 2004, J MED MICROBIOL, V53, P965, DOI 10.1099/jmm.0.45634-0