350 rub
Journal №10 for 2012 г.
Article in number:
Clinical Prospects of Matrix Metalloproteinases 2, 7, 9 and Their Tissue Inhibitors Study in Colorectal Cancer Patients
Keywords: matrix metalloproteinase 2 matrix metalloproteinase 7 matrix metalloproteinase 9 tissue matrix metalloproteinase inhibitors colorectal cancer
Authors:
E.A. Korotkova, E.S. Gershtein, V.V. Prorokov
Abstract:
Extracellular matrix degradation in tumor tissue catalyzed by matrix metalloproteinases (MMP) is one of the key mechanisms initiating cancer invasion, metastasizing, and neoangiogenesis. MMP-2, 7, 9 and their type 1 and 2 tissue inhibitors (TIMP) levels were measured with standard ELISA kits in tumor extracts and blood plasma obtained before and 5-27 after surgery from 99 colorectal cancer (CRC) patients. Rectal cancer was diagnosed in 35, colon cancer - in 64 patients. 6 patients had stage I, 38 - stage II, 28 - stage III, and 28 - stage IV disease. All stage I-III patients were radically operated. Stage IV patients underwent cytoreductive surgery. The content of all MMPs and TIMPs studied was highly significantly elevated in the tumors as compared to histologically unchanged adjacent mucosa: MMP-2 in 90% (р < 0,00001), ММП-7 - in 88 % (p<0,00001), MMP-9 - in 83 % (p<0,001), TIMP-1 - in 92 % (р < 0,00001), and TIMP-2 - in 73 % (р < 0,05) of the patients. No significant associations were revealed between their tumor levels and main CRC clinicopathologic features. Pre-surgical plasma MMP-7 concentration was significantly higher (р < 0,001) and TIMP-1 concentration lower (р < 0,0001) than in control group. Diagnostic sensitivity of plasma MMP-7 comprised 71 % at 70 % specificity level. After surgery a further increase of MMP-7 and normalization of TIMP-1 level were observed. MMP-9 and TIMP-1 plasma levels were lower in patients with lymphogenic metastases than in patients without lymph node involvement, and MMP-7 and TIMP-1 levels were increased in patients with distant hematogenic metastases. Analysis of 5-year follow-up results demonstrated independent unfavorable prognostic role of high plasma MMP-7 and TIMP-1 in CRC with cut-off levels 4.0 and 347 ng/ml respectively. Univariate analysis also revealed unfavorable prognostic value of high (>7,8 ng/mg protein) tumor MMP-7 content in patients with disseminated process.
Pages: 41-46
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