Rap1 GTP酶激活蛋白1、基质金属蛋白酶2与基质金属蛋白酶9在结直肠癌中的表达及其意义

Expression of Rap1 GTPase-activating protein 1, matrix metalloproteinase 2 and matrix metalloproteinase 9 in colorectal carcinoma and their significance

目的 探讨Rap1 GTP酶激活蛋白1（Rap1GAP）、基质金属蛋白酶2（MMP-2）与基质金属蛋白酶9（MMP-9）在结直肠癌中的表达及其与临床病理特征的关系。方法 采用免疫组织化学法检测Rap1GAP、MMP-2与MMP-9在结直肠癌、绒毛状腺瘤、管状腺瘤及正常结直肠组织中的表达，分析各组间表达的差异及与临床病理参数的关系。结果 Rap1GAP在结直肠癌、绒毛状腺瘤、管状腺瘤和正常结直肠组织中的阳性率分别为30.4 %（14／46）、77.8 %（14／18）、69.6 %（16／23）、95.2 %（20／21），各组间表达差异有统计学意义（χ^2＝30.659，P＝0.000）；MMP-2的阳性率分别为71.7 %（33／46）、55.6 %（10／18）、52.2 %（12／16）、9.5 %（2／21），各组间表达差异有统计学意义（χ^2＝22.459，P＝0.000）；MMP-9的阳性率分别为76.1 %（35／46）、61.1 %（11／18）、56.5 %（13／23）、14.3 %（3／21），各组间表达差异有统计学意义（χ^2＝22.643，P＝0.000）。在结直肠癌中，Rap1GAP阳性率与肿瘤分化程度有关（χ^2＝5.275，P＝0.022），与患者性别、年龄及淋巴结转移无关（均P＞0.05）；MMP-2、MMP-9阳性率与淋巴结转移有关（χ^2＝6.661，P＝0.010；χ^2＝8.475，P＝0.040），与患者性别、年龄、分化程度均无关（均P＞0.05）。在结直肠癌中，Rap1GAP的表达与MMP-2及MMP-9呈负相关（r＝-0.424，P＝0.003；r＝-0.294，P＝0.048）；MMP-2和MMP-9的表达无相关性（r＝0.101，P＝0.505）。结论 Rap1GAP、MMP-2与MMP-9在结直肠癌的恶性生物学行为中起重要作用。在结直肠癌中，Rap1GAP与MMP-2和MMP-9的表达呈负相关，三者相互作用影响着结直肠癌的发生、发展。

Objective To investigate the expression of Rap1 GTPase-activating protein 1 （Rap1GAP）,matrix metalloproteinase 2 （MMP-2） and matrix metalloproteinase 9 （MMP-9）, and their relation with clinical patterns in colorectal carcinoma. Methods Immunohistochemistry was used to detect the expression of Rap1GAP,MMP-2 and MMP-9 in colorectal carcinoma, villous adenoma, tubular adenoma and normal colorectal tissue, and their relationship with clinicopathological parameters was analyzed. Results The positive rate of Rap1GAP expression was 30.4 % （14/46）, 77.8 % （14/18）, 69.6 % （16/23） and 95.2 % （20/21） in colorectal carcinoma, villous adenoma, tubular adenoma, and normal colorectal tissue, respectively （χ^2 = 30.659, P = 0.000）. The figures were 71.7 % （33/46）, 55.6 % （10/18）, 52.2 % （12/16） and 9.5 % （2/21） for the positive rate of MMP-2 expression （χ^2 = 22.459, P = 0.000）, as well as for 76.1 % （35/46）, 61.1 % （11/18）, 56.5 % （13/23） and 14.3 % （3/21） for the positive rate of MMP-9 expression, respectively （χ^2 = 22.643, P = 0.000）. In patients with colorectal carcinoma, the expression of Rap1GAP was correlated with tumor differentiation （χ^2 = 5.275, P = 0.022）, but not sex, age, or lymphatic metastasis （all P 〉 0.05）. The expression of MMP-2 and MMP-9 were correlated with lymphatic metastasis （χ^2 = 6.661, P = 0.010; χ^2 = 8.475, P = 0.040）, but not sex, age or tumor differentiation（all P 〉 0.05）. There was a negative correlation between expression of Rap1GAP and MMP-2, MMP-9 in colorectal carcinoma,respectively （r = -0.424, P = 0.003; r = -0.294, P = 0.048）, but no correlation between the expression of MMP-2 and MMP-9 （r = 0.101, P = 0.505）. Conclusions Rap1GAP, MMP-2 and MMP-9 play important roles in the malignant biological behavior of colorectal carcinoma, and the expression of Rap1GAP is negatively correlated with MMP-2 and MMP-9.The interactions among the three affect the occurrence and development of colorectal carcinoma.