The Expression Of MMP-11 And IGF-1 In Gastric Carcinoma And Its Relationship With Invasion And Metastasis

Background:Gastric cancer is a common malignancy with high mortality,Gastric cancer invasion and metastasis are the main factors affected prognosis of patients,tumor invasion and metastasis includ process of tumor cell adhesion,movement,matrix degradation and the formation of new blood vessels,etc,and its molecular mechanism involves a large number of metastasis-associated genes,oncogenes and the suppression oncogenes,such as changes in tumor are currently a hot and a difficult research areas. Therefore,to explore the molecular mechanisms of invasion and metastasis of gastric cancer,and to search gastric cancer invasion and metastasis-related biomarker of gastric cancer has been one of the basic and clinical research topics.Family of matrix metalloproteinases(MMPs) expressed in much of the tumor is closely related to occurrence,invasion and prognosis of tumor.MMPs participates not only in matrix(ECM) degradation,but also in the tumor cell adhesion and the dynamic impact,and the occurrence of tumor,invasion and metastasis.Mmp-11 belong to MMP family mesenchymal lysin(Stromelysin),Few international studies,suggest its mechanism may be through the IGF-1 to participate and influence the tumor occurrence and process(including anti-apoptosis,cell value increment,cell adhesion,angiogenesis process).Objective:Real-time fluorescence quantitative PCR was Applicated to detect MMP-11 relative expression in non-tumor gastric mucosa,primary gastric cancer and gastric cancer metastasis to study its relationship with invasion and metastasis of gastric cancer; On this basis,the chip-based organizations Immunohistochemical analysis of 436 cases of gastric cancer tissues and 92 cases of non-tumor gastric tissues of MMP-11 and IGF-1 was used to explore them with the relationship between gastric cancer invasion and metastasis.Methods:1.Real-time fluorescence quantitative PCR(RT-PCR) was applied to test specimens of 34 patients total 59 cases of fresh specimens,59 cases of fresh specimens including primary gastric cancer 24 cases of lesions,25 cases of gastric cancer metastasis(one of 16 cases of lymph node metastases and 9 cases of peritoneal metastases),detected MMP-11 mRNA relative expression levels in non-tumor gastric mucosa,gastric primary tumor and metastatic lesions in the relative expression.2.The immunohistochemical detection was applied to 436 cases of gastric cancer tissue specimens and 92 cases of paraffin adjacent non-tumor gastric mucosa specimens to detect MMP-11 and IGF-1 in the non-tumor gastric mucosa and gastric cancer tissue differences expression,approaching these gene expression and the relationship between gastric cancer invasion and metastasis. Results:RT-PCR results indicated that MMP-11 was expressed in normal gastric mucosa, gastric cancer tissues and also in metastasis tissues,the expression of gastric primary tumors and metastases compared with non-tumor gastric mucosa increased significantly (P＜0.05).Immunohistochemical analysised that MMP-11 and IGF-1 in gastric cancer are mostly middle or strong positive expression,whereas in non-tumor gastric mucosa, the expression of negative or weak positive expression(P＜0.05).Elderly patients with tumor larger than 5CM,in poorly differentiated,Lauren classification as diffuse type, T3-T4 period,have vascular violations,have lymph node metastasis,have liver and peritoneal metastasis,tumor near the cardia of the stageⅢandⅣgastric carcinoma MMP-11 protein expression was stronger in younger patients,less than tumor 5CM, well-differentiated,Lauren classification for the intestinal type,T1-T2 period, non-vascular violations,no lymph node metastasis without liver and peritoneal metastasis,tumor near the pylorus,ⅠandⅡstage of gastric carcinoma.Elderly patients with tumor larger than 5CM,Lauren classification as diffuse type,T3-T4 period,have vascular violations have lymph node metastasis,have liver and peritoneal metastasis,tumor near the cardia of the stageⅢandⅣgastric cancer tissue IGF-1 protein expression was significantly stronger than younger patients,less than tumor 5CM,Lauren classification for the intestinal type,T1-T2 period,non-vascular violations, no lymph node metastasis without liver and peritoneal metastasis,tumor near the pylorus,ⅠandⅡperiod of gastric cancer organizations.MMP-11 and IGF-1 between the intensity of positive expression was a significant positive correlation(P＜0.01). MMP-11 and IGF-1 in patients with high expression of the average survival time and 5-year survival rate was significantly lower than that of patients with low expression(P＜0.01). Conclusion:1.MMP-11 mRNA related the occurrence and development of gastric cancer.2.MMP-11 and IGF-1 protein expression is closely related,suggesting IGF-1 are downstream effects factor of MMP-11,MMP-11 may be through the IGF-1 pathway participate in gastric cancer procession.3.MMP-11 United IGF-1 involved in the process of invasion and metastasis of gastric cancer.4.MMP-11 and IGF-1 expression could be used as important reference indicator the of gastric biological behavior,and closely relate to Prognosis...