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[Expression of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in the hepatocellular carcinomas].
Hunan Yi Ke Da Xue Xue Bao. 2003 Jun; 28(3):212-6.HY

Abstract

OBJECTIVE

To explore the expression and clinical prognostic significance of matrix metalloproteinase-2 mRNA (MMP-2 mRNA), tissue inhibitor of matrix metalloproteinase-2 mRNA (TIMP-2 mRNA), matrix metalloproteinase-2 protein (MMP-2), matrix metalloproteinase-9 protein (MMP-9), tissue inhibitor of matrix metalloproteinase-1 protein (TIMP-1), and tissue inhibitor of matrix metalloproteinase-2 protein (TIMP-2) in the hepatocellular carcinomas (HCCs).

METHODS

Fifty-six specimens of HCCs from 56 patients, who were followed-up, were investigated by in situ hybridization with specific probes for MMP-2, TIMP-2, and by immunohistochemistry with anti-MMP-2, MMP-9 and anti-TIMP-1, TIMP-2 monoclonal antibody. We analyzed the data with chi-square test, spearmans correlation analysis, monovariate Kaplan-Meier plot and multivariate Cox regression analysis.

RESULTS

1. The positive expression of MMP-2mRNA, TIMP-2mRNA, MMP-2 protein, MMP-9 protein, TIMP-1 protein and TIMP-2 protein in the 56 HCCs cases were 48 (85.7%), 35 (62.5%), 44 (78.6%), 41 (73.2%), 30 (53.6%), and 38 (68%), respectively. 2. We found over-expression of MMP-2 mRNA, MMP-2 protein, and MMP-9 protein, but low expression of TIMP-1 protein in the 56 cases of HCCs (P < 0.01, P < 0.05). 3. There was a positive association between TIMP-2mRNA and TIMP-2 protein expression, and between MMP-2 mRNA and MMP-2 protein in HCCs, respectively (r = 0.316, P < 0.05; r = 0.356, P < 0.05). 4. Over-expression of MMP-2 mRNA was positively correlated to the tumor size and TNM classification (r = 0.441, P < 0.001; r = 0.340, P < 0.05), and MMP-9 protein was related to shortened survival (P < 0.05). 5. In both monovariate Kaplan-Meir plot and multivariate Cox regression analysis, the expression of MMP-2 protein and MMP-9 protein were linked to unfavorable prognosis. These results were further confirmed by multivariate analysis in which MMP-2 protein and MMP-9 protein emerged as independent prognostic factors for poor survival regardless of the age, tumor size, tumor grades, TNM classification and expression of MMP-2mRNA, TIMP-2mRNA, TIMP-1 protein and TIMP-2 protein. The hazard ratios of expression of MMP-2 protein and MMP-9 protein were 3.875 and 4.528, respectively.

CONCLUSION

The over-expression of MMP-2mRNA, MMP-2 protein and MMP-9 protein and the imbalance between MMP-2 and TIMP-2 play pivotal roles in the degradation of excellular matrix of HCCs. MMP-2 and MMP-9 immunoreactive protein have been closely related to a shortened survival independent of major prognostic indicators in the primary HCC and increase the risk of the patients after the operation.

Authors+Show Affiliations

Wei QY
Department of Pathology, Second Xiangya Hospital, Central South University, Changsha 410011, China.
Wu YQ
No affiliation info available
Fan SQ
No affiliation info available

MeSH

AdultAgedBiomarkers, TumorCarcinoma, HepatocellularFemaleHumansLiver NeoplasmsMaleMatrix Metalloproteinase 2Matrix Metalloproteinase 9Middle AgedMultivariate AnalysisPrognosisProtease InhibitorsRNA, MessengerTissue Inhibitor of Metalloproteinase-1Tissue Inhibitor of Metalloproteinase-2

Pub Type(s)

English Abstract
Journal Article

Language

chi

PubMed ID

14653069

Citation

Wei, Qi-you, et al. "[Expression of Matrix Metalloproteinases and Tissue Inhibitors of Matrix Metalloproteinases in the Hepatocellular Carcinomas]." Hunan Yi Ke Da Xue Xue Bao = Hunan Yike Daxue Xuebao = Bulletin of Hunan Medical University, vol. 28, no. 3, 2003, pp. 212-6.
Wei QY, Wu YQ, Fan SQ. [Expression of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in the hepatocellular carcinomas]. Hunan Yi Ke Da Xue Xue Bao. 2003;28(3):212-6.
Wei, Q. Y., Wu, Y. Q., & Fan, S. Q. (2003). [Expression of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in the hepatocellular carcinomas]. Hunan Yi Ke Da Xue Xue Bao = Hunan Yike Daxue Xuebao = Bulletin of Hunan Medical University, 28(3), 212-6.
Wei QY, Wu YQ, Fan SQ. [Expression of Matrix Metalloproteinases and Tissue Inhibitors of Matrix Metalloproteinases in the Hepatocellular Carcinomas]. Hunan Yi Ke Da Xue Xue Bao. 2003;28(3):212-6. PubMed PMID: 14653069.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - [Expression of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in the hepatocellular carcinomas]. AU - Wei,Qi-you, AU - Wu,Yuan-qing, AU - Fan,Song-qing, PY - 2003/12/5/pubmed PY - 2004/5/15/medline PY - 2003/12/5/entrez SP - 212 EP - 6 JF - Hunan yi ke da xue xue bao = Hunan yike daxue xuebao = Bulletin of Hunan Medical University JO - Hunan Yi Ke Da Xue Xue Bao VL - 28 IS - 3 N2 - OBJECTIVE: To explore the expression and clinical prognostic significance of matrix metalloproteinase-2 mRNA (MMP-2 mRNA), tissue inhibitor of matrix metalloproteinase-2 mRNA (TIMP-2 mRNA), matrix metalloproteinase-2 protein (MMP-2), matrix metalloproteinase-9 protein (MMP-9), tissue inhibitor of matrix metalloproteinase-1 protein (TIMP-1), and tissue inhibitor of matrix metalloproteinase-2 protein (TIMP-2) in the hepatocellular carcinomas (HCCs). METHODS: Fifty-six specimens of HCCs from 56 patients, who were followed-up, were investigated by in situ hybridization with specific probes for MMP-2, TIMP-2, and by immunohistochemistry with anti-MMP-2, MMP-9 and anti-TIMP-1, TIMP-2 monoclonal antibody. We analyzed the data with chi-square test, spearmans correlation analysis, monovariate Kaplan-Meier plot and multivariate Cox regression analysis. RESULTS: 1. The positive expression of MMP-2mRNA, TIMP-2mRNA, MMP-2 protein, MMP-9 protein, TIMP-1 protein and TIMP-2 protein in the 56 HCCs cases were 48 (85.7%), 35 (62.5%), 44 (78.6%), 41 (73.2%), 30 (53.6%), and 38 (68%), respectively. 2. We found over-expression of MMP-2 mRNA, MMP-2 protein, and MMP-9 protein, but low expression of TIMP-1 protein in the 56 cases of HCCs (P < 0.01, P < 0.05). 3. There was a positive association between TIMP-2mRNA and TIMP-2 protein expression, and between MMP-2 mRNA and MMP-2 protein in HCCs, respectively (r = 0.316, P < 0.05; r = 0.356, P < 0.05). 4. Over-expression of MMP-2 mRNA was positively correlated to the tumor size and TNM classification (r = 0.441, P < 0.001; r = 0.340, P < 0.05), and MMP-9 protein was related to shortened survival (P < 0.05). 5. In both monovariate Kaplan-Meir plot and multivariate Cox regression analysis, the expression of MMP-2 protein and MMP-9 protein were linked to unfavorable prognosis. These results were further confirmed by multivariate analysis in which MMP-2 protein and MMP-9 protein emerged as independent prognostic factors for poor survival regardless of the age, tumor size, tumor grades, TNM classification and expression of MMP-2mRNA, TIMP-2mRNA, TIMP-1 protein and TIMP-2 protein. The hazard ratios of expression of MMP-2 protein and MMP-9 protein were 3.875 and 4.528, respectively. CONCLUSION: The over-expression of MMP-2mRNA, MMP-2 protein and MMP-9 protein and the imbalance between MMP-2 and TIMP-2 play pivotal roles in the degradation of excellular matrix of HCCs. MMP-2 and MMP-9 immunoreactive protein have been closely related to a shortened survival independent of major prognostic indicators in the primary HCC and increase the risk of the patients after the operation. SN - 1000-5625 UR - https://www.unboundmedicine.com/medline/citation/14653069/[Expression_of_matrix_metalloproteinases_and_tissue_inhibitors_of_matrix_metalloproteinases_in_the_hepatocellular_carcinomas]_ DB - PRIME DP - Unbound Medicine ER -
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