结肠直肠癌病人血浆金属蛋白酶及其组织抑制物的表达及意义

Expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in plasma of patients with colorectal carcinoma

目的:探讨结肠直肠癌病人血浆中基质金属蛋白酶-9(MMP-9)及其组织抑制因子-1(TIMP-1)的表达与结肠直肠癌浸润、转移及预后的关系,以及手术、化疗对其表达的影响,以期在分子水平上更准确地判断结肠直肠癌的预后。方法:选取结肠直肠癌病人50例,于手术前、术后10d、6次化疗后2周,分别抽取病人4mL外周静脉血,采用酶联免疫分析法检测MMP-9、TIMP-1血浆浓度的变化。结果:低分化结肠直肠癌病人血浆MMP-9及TIMP-1水平高于高、中分化者(P<0.01、P<0.05);TNMⅢ、Ⅳ期病人高于TNMⅠ、Ⅱ期者(P<0.01)。手术后血浆MMP-9、TIMP-1水平显著下降,有统计学意义(P<0.01、P<0.05),化疗后其浓度变化无显著性差异(P>0.05)。结论:MMP-9和TIMP-1与肿瘤恶性程度有关;术前检测外周血MMP-9和TIMP-1浓度有可能成为结肠直肠癌辅助诊断及病情评估的较好血清学标志。MMP-9可能与肿瘤复发或转移存在一定关系,术后动态检测外周血MMP-9浓度可反映肿瘤负荷,从而对监测肿瘤复发提供一定帮助。

Objectives To investigate the expression of matrix metalloproteinases-9（MMP-9） and its tissue inhibitor of metal loproteinases-1 （TIMP-1） in plasma of patients with colorectal carcinoma, in order to reveal its relationship with the invasion, metastasis and prognosis of the tumor, Methods Plasma concentrations of MMP-9 and TIMP-1 were measured by ELISA assay in 50 patients with colorectal carcinoma pre- and postoperatively; their relationship with clinicopathologic manifestations was analyzed. Results The concentration levels of MMP-9 and TIMP-1 in the patients with poorly differentiated tumors and those in TNM Ⅲ or Ⅳ stages were significantly higher than in cases with well differentiated tumors and those in TNM Ⅰ or Ⅱ stages （P〈0.01）. The concentration levels decreased obviously after operation （PMMP-9〈0.01, PTIMP-1〈0.05）, while there were no significant changes after chemotherapy. Conclusions The expression levels of MMP-9 and TIMP-1 were both significantly correlated with the degree of malignancy and biological behavior of the carcinoma. Higher levels of MMP-9 means worse prognosis in patients with carcinoma. Detecting the expression of MMP-9 and TIMP-1 may be useful in predicting the biological behavior and prognosis of colorectal carcinoma.