MMP-9及TIMP-1表达与大肠癌浸润转移及预后的相关性研究

目的探讨基质金属蛋白酶-9(MMP-9)及其抑制物(TIMP-1)表达与大肠癌浸润、转移及预后的关系,以期在分子水平上更准确判断大肠癌患者的预后及为寻找相应的基因治疗方法提供依据。方法采用免疫组织化学染色的方法检测54例大肠癌组织标本中MMP-9及TIMP-1的表达情况,并以大肠腺瘤组织标本15例作为对照。结果MMP-9的表达率在大肠癌中为70.4%,高于大肠腺瘤的33.3%(P<0.05)。其表达与大肠癌的浸润深度、Dukes分期、淋巴结转移及生存期均密切相关(P<0.05)。TIMP-1的表达在大肠腺瘤及大肠癌组织中没有显著性差异(P>0.05),但其表达与大肠癌组织学类型、分化程度、淋巴结有无转移密切相关,对预后无显著性影响(P>0.05)。大肠癌MMP-9和TIMP-1蛋白表达存在显著正相关(r=0.374,P<0.01)。结论MMP-9及TIMP-1对大肠癌浸润、转移均有明显影响。MMP-9蛋白阳性表达促进大肠癌浸润和转移,患者预后差。MMP-9和TIMP-1的检测可以作为临床判断大肠癌的恶性程度、转移及估计预后的重要参考指标。

Association among the expressions of MMP-9, TIMP-1 and invasion, metastasis and prognosis in colorectal carcinoma

Objective To investigate the association among the expressions of matrix metalloproteinases-9(MMP-9),tissue inhibitor of metalloproteinases-1(TIMP-1) and tumor biological characteristics and survival rate of patients with colorectal cancer.We hope to offer the foundation of the treatment in colorectal cancer in order to determine the prognosis of patients more accurately and look for the way of related gene therapy in molecular level.Methods Immunoperoxidase staining of MMP-9 and TIMP-1 was performed using 54 samples with colorectal carcinoma,acquiring from the patients who received radical resection for colorectal carcinoma from January 1997 to December 1998 in our hospital,and the colorectal adenoma biopsy specimens were obtained from 15 controls under clinical coloscopy.Results The expression rate of MMP-9 was 33.3% in colorectal adenoma and 70.4% in colorectal cancer;the later has closed correlation with invasion depth,Dukes stages,metastasis of lymph node and prognosis(P<0.05).No significant difference in expression of TIMP-1 between colorectal abenoma and colorectal cancer(P>0.05),but there was significant relationship among TIMP-1 expression and histological type,cellular differentiation and metastasis of lymph node,whereas its expression has no significant effect on prognosis(P>0.05).There was significant positive correlation between the expressions of MMP-9 and TIMP-1 in colorectal cancer(r=0.374,P<0.05).Conclusions The expressions of MMP-9 and TIMP-1 all have significant effects on the turmor biological behavior in colorectal cancer.There were worse prognoses in patients with positive expression of MMP-9.To detect the expressions of MMP-9 and TIMP-1 may be helpful for judging tumor biological behavior and prognosis in colorectal carcinoma.