TIMP-3Gene Methylation And The Expression Level And Significance Of MMP-3Protein And TIMP-3Protein In Colon Cancer Tissue

ObjectiveTo investigate the relationship between the protein expression status of MMP-3and TIMP-3in colonic cancer, adenoma of colon and normal colon tissues, and the5’CpG island methylation status of TIMP-3gene promoter and clinicopathological parameters. To analyse the potential association between the promoter methylation of TIMP-3gene and its protein expression status. So that we can further understand the molecular mechanism of the pathogenesis of colonic cancer, which can provide some theoretical and experimental basis for the early diagnosis and clinical treatment at the molecular level.MethodsTumours from43patients with colonic cancer,40patients with adenoma of colon and40normal colonic tissues (5cm far from the cancer tissue) were investigated for the expression of MMP-3and TIMP-3proteins by immunohistochemistry. Tumours from43patients with colonic cancer and40normal colonic tissues were investigated for the methylation detection of TIMP-3gene promoter by methylation specific polymerase chain reaction (MSP).ResultsImmunohistochemical results show that the positive expression ratio of MMP-3in colon cancer was67.4%(29/43), which was significantly higher than th at in colonic adenoma (the ratio was45%,18/40) and distal colonic cancer normal tissues (the ratio was12.5%,5/40). The positive expression ratio of TMP-3in colon cancer was25.6%(11/43), which was significantly lower than that in colonic adenoma (the ratio was47.5%,19/40) and distal colonic cancer normal tissues (the ratio was72.5%,29/40). The proteins expression status of MMP-3and TIMP-3in colon cancer were significantly associated with TNM stage, lymph node metastasis and differentiation (P＜0.05), but not associated with patients’ gender and age,(P＞0.05). There was negative correlation between the protein expression of MMP-3and TIMP-3in colon cancer group (r=-0.503, P=0.001).The TIMP-3promoter was aberrant methylated in colon cancer (the ratio was60.5%,26/43), but not in normal tissues. The methylation status of TIMP-3gene were significantly associated with TNM stage, lymph node metastasis, and differentiation of cancer cell (P＜0.05), but not with patients’ gender and age (P＞0.05). Promoter methylation of TIMP-3gene was negatively correlated to its protein expression (r=-0.398, P=0.009).Conclusions(1) The protein expression ratio of MMP-3in colon cancer group was significantly higher than that in adenoma group and normal group. which indicate that MMP-3proteins may play an important role in the pathogenesis of colonic cancer.(2) The protein expression ratio of TIMP-3in colon cancer group was significantly lower than that in adenoma group and normal group. which indicate that TIMP-3proteins may play an important role in the pathogenesis of colonic cancer. which indicate that MMP-3and TIMP-3proteins may play an important role in the pathogenesis of colonic cancer.(3) Expression of MMP-3high expression and TIMP-3low expression protein in colon cancer were not significantly associated with patients’ gender an d age, but with TNM stage, lymph node metastasis, and differentiation of cancer cell,(4) There was negative correlation between the protein expression of MMP-3and TIMP-3in colon cancer group, which indicate that MMP-3and TIMP-3may play an opposite role in the pathogenesis of colonic cancer.(5) The promoter methylation ratio of TIMP-3gene in colon cancer is higher. And there was negative correlation between the methylation status of TIMP-3and its protein expression in colon cancer, which suggest that the gene methylation down-regulate its protein expression.