Expression Of MRNA And Protein In Gastric Cancer By Tissue Microarray And Their Clinical Significance

Gastric cancer is one of the most common malignant tumors in China. Although a declined incidence has been observed in recent years, the gastric cancer still contributed to the highest mortality among the malignant tumors. Most of the patients with gastric cancer die from tumor invasion, metastasis and recurrence. It is necessary to search for potential prognostic factors that help to predict the prognosis of the patients,and to guide for prognostic factors tha help to predict the prognosis of the patients,and to give guides for personalized treatment and to enhance long-term survival.The occurrence, development and metastasis of tumor are complex pathologic processes, involving multi-stages evolution and multi-genes modulation. Study of the molecular mechanism of tumor,the learning about the related genes in different phases during development of tumor,and the detecting of the expressions of these genes on mRNA and/or protein levels,have become the hot spots,which are contribute to molecular pathological diagnosis,judgement of clinical prognosis and selection of treatment plans.There have been many genes observed participating the development of gastric cancer, for example,EGFR,bFGF,E-CD and MDR1.The expression of each gene takes place under the background or other genes expressions. MMP-2, matrix metalloproteinase-2, can degradate extracellular matrix.TIMP-2, tissue inhibitor of metalloproteinase-2, has opposite role in gastric cancer. The two genes have different roles in different tumors.In this paper, tissue chip(TC), also named tissue microarray(TMA) was utilized. TC is a newly developed molecular biologic technique based on cell morphology.It provides a high-flux,multi-samples and quick analysis tool for molecular biology.In this study,tumor tissue specimens were taken from 210 cases gastric cancer patients. 94 cases of them were operated in the first hospital of Shaoxing between 1995 and 2000,116 cases in the first affiliated hospital of school of medicine,Zhejiang University in 2001. Expression of MMP-2 and TIMP-2 were examined by in situ hybridization and immunohistochemistry.SPSS 15.0 software was used for statistical analysis .The statistical methods used included X~2 test,. Spearman rank correlation analysis,Kaplan-Meier survival curve analysis and log rank test. The level of . statistics is significant in P <0.05.The results of hybridization in situ indicated that 65.2% and 26.2% of the 210 cases were detected MMP-2 mRNA and TIMP-2 mRNA positive. Firstly,there were significant relationships of MMP-2 mRNA expression, with tumor diameter(r=0.150,P=0.025 ),invasion depth( r =0.391. P =0.000.).vessel invasion (r =0.192, P =0.004) ,lymph node (r =0.207, P =0.002) ,and distant metastasis (r =0.153, P =0.022) . Secondly,there were significant negative relationships of TIMP-2 mRNA expression with tumor diameter (r =-0.171, P =0.011,invasion depth (r =-0.194, P =0.004) ,vessel invasion (r =-0.268, P =0.000) ,lymph node (r =0.207, P =0.002) and distant metastasis (r =-0.197, P =0.003) . Thirdly, there was a negative relationship of MMP-2 mRNA and TIMP-2 mRNA expression. The mean survival time in MMP-2 mRNA positive expression cases was significantly shorter than MMP-2 mRNA negative expression. The mean survival time in TIMP-2 mRNA negative expression cases was significantly shorter than TIMP-2 mRNA positive expression.The results of immunohistochemistry indicated that revealed that70.5% and 32.4% of the 210 cases were detected MMP-2 protein and TIMP-2 protein positive. Firstly, there were significant relationships of MMP-2 protein expression with tumor diameter (r=0.335, P =0.000),invasion depth(r =0.201, P =0.003 ),vessel invasion(r=0.300, P =0.000),lymph node(r=0.169, p =0.012) and distant etastasis (r =0.167, P =0.013) . Secondly,there were significant negative relationships of TIMP-2 protein expression with tumor diameter (r=-0.335, P =0.000) ,invasion depth (r =-0.355, P =0.000) ,vessel invasion (r =-0.205, P =0.002) ,lymph node (r =-0.166, P =0.013) and distant metastasis(r =-0.228 , P =0.001). Thirdly, there was a negative relationship of MMP-2 protein and TIMP-2 protein expression, the mean survival time in cases with MMP-2 protein positive expression was significantly shorter than those no MMP-2 protein expression. the mean survival time in cases with MMP-2 protein negative expression was significantly higher than those no TIMP-2 protein expression.In conclusion, this study revealed that MMP-2 and TIMP-2 might be involved in the growth,invasion and metastasis of gastric cancer. The expression patterns of MMP-2 and TIMP-2 have significant influence on the prognosis of gastric cancer, patients. Immunostaining for levels of MMP-2 and TIMP-2 expression by tissue microarray assay can be used as professional prognostic markers and genetic treatment indicators for gastric cancer patients.