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Expression Of MMP-2 And MMP-9 MRNA And The Relationship With Invasion And Metastasis In Human Hepatocellular Carcinoma

Posted on:2002-08-09Degree:MasterType:Thesis
Country:ChinaCandidate:H D ZhangFull Text:PDF
GTID:2144360032950105Subject:Surgery
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Background and PurposePrimary hepatocellular carcinoma (HCC), as one of the most common malignant tumors in the world, with the incidence rate still rising, remains a poor prognosis, despite of the improvement of modern diagnostic and therapeutic modalities. To a great extent, it is because of intrahepatic invasiveness and distant metastasis, which usually results in the difficulty of radical resection and leads to postoperative recurrence. Therefore, it is very necessary to find some novel tumor markers in order to accurately evaluate the possibility of metastasis and the prognosis. To its pathological characteristics, as we know,HCCs are generally associated with abundant extracellular matrix (ECM), and about 80% of HCCs are encapsulated with fibrous connective tissues. In view of this, the degeneration of ECM and penetration of basement membrane is a key point step in the procedure of invasion and metastasis of HCCs, where the matrix metalloproteinase (MMPs) plays the leading role.Matrix metalloproteinases are a family of enzymes whose main function is degradation of the extracellular matrix.MMPs have been defined functionally as having the following characteristics: (l)they are proteinases that drgrade at least one component of the extracellular matrix; (2)they contain a zinc ion and are inhibited by chelating agents; (3)they are secreted in a latent form.requiring activation for proteolytic activity;(4)they are inhibited by tissue inhibitors of metalloproteinases (TIMPs); and (5)they share common amino acid sequences.MMP-2 (gelatinase A) and MMP-9 (gelatinase B) are the main matrix metalloproteinases in decomposing collagen include type IV and V in the matrix, because collagen IV not only exists in the ECM, but also is one of the most important components of the basement membrane. Besides the structure proximity between MMP-2 and MMP-9 gene, the latter has a specific sequence of 48 bases which cannot be found in other MMPs, and this discrepancy may leads to the different expression in HCC and the nontumoral tissue.In this study, expression of MMP-2 and MMP-9 mRNA in HCC was detected respectively by reverse transcription polymerase chain reaction (RT-PCR) using specific primers, the quantitative RT-PCR assessment was established to gauge MMP-2 and MMP-9 mRNA levels in HCC. The correlations between the expression and clinicopathologic variables, and the different expression between themselves were studied too.MethodsSpecimens of 28 tumors and corresponding nontumoral liver tissues wereobtained, and B-actin internal standard system was established for comparative PCR. For analysis of MMP-2 and MMP-9 mRNA level in HCC, each tumor sample was compared with its corresponding nontumoral pair, assessing the absorbency of MMP-2 and MMP-9. All data were analyzed using SSPS 10.0, statistical significance were defined as a P value <0.05.Results1. The expression of MMP-2 mRNA in HCC and the corresponding nontumoral tissues were positive, the former is significantly higher than the latter (p<0.01). And there was no significant correlation between the expression level and preoperative AFP level, tumor size, TNM staging, and whether being associated with portal vein tumor thrombus (P>0.05).2. The expression of MMP-9 mRNA in HCC and the corresponding nontumoral tissues were positive, the former is significantly higher than the latter (p<0.01). And there was no significant correlation between the expression level and preoperative AFP level, tumor size, TNM staging(P>0.05). However, there was a significant correlation between the expression level and the existence of portal vein tumor thrombus (PO.01).3. There was a significant difference in the expression level in HCC between MMP-2 and MMP-9 (P<0.01), and it was proved to be a close positive correlation by the correlation test (P<0.01).Conclusions1. The MMP-2 mRNA level in HCC is higher than that in the nontumoral tissue, it indicates a close correlation between MMP-2 and the malignant biological behavior of HCC.2...
Keywords/Search Tags:hepatocellular carcinoma, matrix metalloproteinase, MMP-2, MMP-9, RT-PCR
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