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Increased expression of matrix metalloproteinase 9 correlates with poor prognostic variables in renal cell carcinoma

 Nam Hoon Cho  ;  Hyo Sub Shim  ;  Sang Ho Cho  ;  Sung Jun Hong  ;  Young Deuk Choi  ;  Sung Hui Hong  ;  Suki Hee Kang  ;  Sun Young Rha 
 EUROPEAN UROLOGY, Vol.44(5) : 560-566, 2003 
Journal Title
Issue Date
Carcinoma, Renal Cell/enzymology* ; Chi-Square Distribution ; Female ; Humans ; Kidney Neoplasms/enzymology* ; Male ; Matrix Metalloproteinase 9/metabolism* ; Matrix Metalloproteinases/metabolism ; Middle Aged ; Prognosis ; Proportional Hazards Models ; Reverse Transcriptase Polymerase Chain Reaction ; Statistics, Nonparametric ; Survival Analysis ; Up-Regulation
MMP2 ; MMP9 ; cDNA array ; RT-PCR ; Zymography ; Renal cell carcinoma
BACKGROUND: MMP2 and MMP9 are two gelatinolytic enzymes, which are key regulators of tumor invasion and metastasis. This study aimed to clarify the prognostic significance of MMP2 and MMP9 with particular regard to their transcript levels, enzymatic activities in renal cell carcinomas (RCCs).

MATERIALS AND METHODS: Through cDNA array, the differential expression of the MMP superfamily was evaluated in RCC. Various properties of MMP2 and MMP9 were quantified, in 178 patients with RCC, based on the Heidelberg classification. Of these, 145 cases including 16 fresh-frozen cases were available for MMP2 and MMP9 transcript level evaluation. In addition, gelatinolytic activity was assessed by zymography in 16 other fresh-frozen samples from new RCC cases.

RESULTS: MMP2, 9, 11, 14, and 16 were upregulated in the conventional RCC in comparison with the chromophobe RCC, whereas MMP1, 11 and 16 were pronounced in papillary RCC. MMP9 transcript levels were strongly associated with the MMP9 enzymatic activity (p=0.001), and therefore, with disease-free survival (p=0.001) and metastasis (p=0.011). Gelatinolytic activity of MMP9 by zymography was strongly associated with MMP9 mRNA expression, which was more intense in 'conventional' RCC than in 'chromophobe' RCC (p=0.001), irrespective of tumor grade or stage. MMP9 was proven to be a significant prognostic predictor by multi-variate survival analysis (p=0.0054). MMP2 enzymatic activity disappeared in spite of its constant transcript expression in RCC.

CONCLUSIONS: MMP9 appears to be regulated at the transcript level, whereas MMP2 is regulated at the posttranscriptional level. Poor survival with a high frequency of metastases in 'conventional' RCC is associated with MMP9, which exhibits a high transcriptional level, and a high gelatinolytic activity. As a result, MMP9 may be a candidate of predictors of disease-free survival in RCC.
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1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Urology (비뇨의학교실) > 1. Journal Papers
Yonsei Authors
Kang, Suki(강숙희) ORCID logo https://orcid.org/0000-0002-9957-3479
Rha, Sun Young(라선영) ORCID logo https://orcid.org/0000-0002-2512-4531
Shim, Hyo Sup(심효섭) ORCID logo https://orcid.org/0000-0002-5718-3624
Cho, Nam Hoon(조남훈) ORCID logo https://orcid.org/0000-0002-0045-6441
Cho, Sang Ho(조상호)
Choi, Young Deuk(최영득) ORCID logo https://orcid.org/0000-0002-8545-5797
Hong, Sung Joon(홍성준) ORCID logo https://orcid.org/0000-0001-9869-065X
Hong, Sung Hui(홍성희)
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