MMP-9和TIMP-1在结肠癌组织中的表达及其临床意义

目的 探讨基质金属蛋白酶9（MMP-9）及组织抑制剂1（TIMP-1）在结肠癌中的表达和临床意义。方法 采用RT-PCR、免疫组化、计算机图象分析方法定量检测200例结肠癌及其对应癌旁组织中MMP-9、TIMP-1 基因和蛋白表达水平，并分析其表达与临床病理特征的关系及两者的相关性。结果 结肠癌组织中MMP-9 mRNA的表达上调者141例（70.5％），癌旁组织为21例（10.5％），差异有统计学意义（P=0.001）。MMP-9 mRNA表达与结肠癌Dukes分期、淋巴结转移及分化程度相关。结肠癌及其癌旁组织中TIMP-1 mRNA表达上调者分别为104例（52.0％）和121例（60.5％），差异无统计学意义（P=0.087）。TIMP-1 mRNA表达与结肠癌临床病理特征均无关。MMP-9蛋白在结肠癌组织中的免疫组织化学染色强度为1.79±0.11，高于癌旁组织的1.22±0.05（P=0.002），MMP-9蛋白表达水平与结肠癌Dukes分期及淋巴结转移相关。TIMP-1蛋白在结肠癌和癌旁组织中表达均较MMP-9蛋白表达弱，其表达与临床病理特征无关。在结肠癌组织中MMP-9与TIMP-1蛋白表达呈负相关 （r=-0.63，P＜0.01）。 结论 MMP-9表达在结肠癌的进展中具有促进作用，而TIMP-1表达则可能具有拮抗作用。

Expression of MMP-9 and TIMP-1 in human colon cancer and its clinical significance

Objective To detect matrix metallopeptidase-9（MMP-9） and tissue inhibitor of metalloproteinase-1（TIMP-1） expression in human colon cancer,and their effect on the progression of human colon cancer.Methods Colon cancer tissues and paired distant normal colon tissues obtained from 200 inpatients were allocated into two groups.The expressions of MMP-9 and TIMP-1 were detected by RT-PCR and immunohistochemical staining and computerized image analysis.The relationship between the two expressions with clinicopathologic characteristics of human colon cancer was investigated by statistical analysis.Results The upregulation of MMP-9 mRNA in tumor and normal tissues were 141（70.5%） and 21（10.5%） respectively（P=0.001）,and the mRNA expression level was correlated with Dukes＇ staging,lymph node status and histological differentiation grade.The upregulation of TIMP-1 mRNA tumor and normal tissues were 104（52.0%） and 121（60.5%） respectively（P=0.087）,and had no correlation to clinical characteristics.The MMP-9 protein positive degree of immunohistochemical staining in tumor tissue was 1.79±0.11,higher than 1.22±0.05 in control group（P=0.002）,and the protein expression was correlated with Dukes＇ staging and lymph node status.The expression of TIMP-1 protein was lower than expression of MMP-9 protein in two groups,and had no correlation with clinical characteristics.Pearson test suggested that protein expressive level of MMP-9 was negatively correlated with TIMP-1 in tumor group（r=-0.63,P0.01）.Conclusion MMP-9 plays an important role in the progression of human colon cancer,and TIMP-1 may have antagonistic effects during the progression of human colon cancer.