胃癌组织C-Met和MMP-11表达与肝转移相关性研究

Expressions of C-Met and MMP-11 in gastric carcinoma and their relation to hepatic metastasis

目的:研究肝细胞生长因子受体C-Met和基质金属蛋白酶MMP-11在胃癌组织中的表达与肝转移间的关系。方法:选取新疆医科大学第一附属医院2002-01-21-2008-12-13收治的胃癌未发生肝转移及同期肝转移患者各78例石蜡样本,分别作为实验组和对照组,采用免疫组织化学及原位杂交方法检测C-Met和MMP-11的mRNA及蛋白表达情况。采用χ2检验的方法对胃癌肝转移的可能危险因素进行单因素统计分析,筛选出胃癌肝转移可能的危险因素,进行Logistic多变量回归分析。指标间相关性分析采用Spearman等级相关分析法。结果:C-Met mRNA和MMP-11mRNA在胃癌组织中的阳性表达率分别为55.13%和56.41%,在肝转移组的阳性率分别为70.50%和75.60%,在非肝转移组的阳性率分别为39.70%和37.20%,两者的阳性率在肝转移组与非肝转移比较,差异均有统计学意义,P值均<0.001;C-Met mRNA、MMP-11mRNA表达与胃癌的脉管侵犯(χ2=4.692,P=0.03;χ2=5.878,P=0.015)、淋巴结转移(χ2=6.914,P=0.009;χ2=10.23,P=0.001)、TNM分期(χ2=4.989,P=0.026;χ2=7.843,P=0.005)相关;其中MMP-11mRNA表达还与胃癌浸润深度相关,χ2=13.9,P<0.001。C-Met和MMP-11蛋白在胃癌组织中的阳性表达率分别为58.97%和57.69%,在肝转移组的阳性表达率分别为67.90%和71.80%,在非肝转移组的阳性表达率分别为50.00%和43.60%,两者的阳性表达率在肝转移组与非肝转移组比较,差异均有统计学意义,P=0.023,<0.001;C-Met和MMP-11蛋白表达与胃癌的淋巴结转移(χ2=5.692,P=0.017;χ2=8.936,P=0.003)和TNM分期(χ2=4.084,P=0.043;χ2=6.779,P=0.009)相关;其中MMP-11蛋白表达还与胃癌浸润深度相关,χ2=4.237,P=0.04。结论:C-Met和MMP-11在胃癌组织中的过表达可能与胃癌肝转移的行为相关,有望为胃癌肝转移的预测提供客观依据。

OBJECTIVE： To investigate the relationship between expression of hepatocyte growth factor receptor C-Met,matrix metalloproteinases MMP-11 and gastric cancer hepatic metastasis. METHODS： Seventy-eight gastric cancer patients with synchronal liver metastasis were selected as experimental group,and 78 cases without synchronal liver metastasis as control group to detect the C-Met,MMP-11 protein and mRNA levels of the two group in immunohistochemis try assay and in situ hybridization assay. The risk factors for single factor statistical analysis was tested by chi square test the possible risk factors for liver metastasis of gastric cancer were screened in logistic multivariate regression analysis. The correlation was anlyzed using Spearman rank correlation analysis. RESULTS：The positive rate of C-Met mRNA, MMP-11 mRNA expressing in gastric cancer were 55. 13%, 56.41% respectively, the positive rate of the expressions in gastric cancer hepatic metastasis group were 70. 50%,75. 60%, the positive rate of the expressions in gastric cancer non-hepatic metastasis group were 39.70 %, 37.20 %, comparing with the non-gastric cancer hepatic metastasis, there were significant deviation （P〈0. 001）. The expression of C-Met mRNA, MMP-11 mRNA correlated with vessel infiltration（x2 = 4. 692, P=0.03;X2 =5. 878,P=0. 015）,lymph node transfusion （X2 =6. 914,P=0. 009;X2 =10.23,P=0. 001）,TNM stage （X2 =4. 989,P=0. 026;X2 =7. 843,P=0. 005）. Of the total,the expression of MMP-11 mRNA correlated with the infiltration depth of gastric cancer（x2= 13.9,P〈0. 001）. The positive rate of C-Met protein, MMP-11 protein expressing in gastric cancer were 58.97%,0,57.69% respectively, the positive rate of their expressing in gastric cancer hepatic metastasis were 67. 90%,71. 80%, the positive rate of the expressions in gastric cancer non-hepatic metastasis were 50. 00%, 43.60%,respectively,comparing with the non-gastric cancer hepatic metastasis group, there were significant deviation （P=0. 023 ;P〈0. 001）. The expression of C-Met protein, MMP-11 protein correlated with lymph node transfusion（X2 = 5. 692,P=0. 017;X2 =8. 936,P=0. 003） and TNM stage （X2 =4. 084,P=0. 043;X2 =6. 779,P=0. 009）. Of the total, the expression of MMP-11 protein correlated with the infiltration depth of gastric cancer（X2 = 4. 237, P= 0.04）. CON- CLUSION：The excessive expression of c-Met and MMP-11 correlated with infiltration and transfusion,particular with hepatic metastasis,and they may provide objective proof for the early prediction of gastric cancer hepatic metastasis.