【作者】 常静；

【导师】 于庭；

【作者基本信息】 吉林大学 ， 临床医学， 2008， 硕士

【摘要】 为了研究基质金属蛋白酶2(MMP-2)和基质金属蛋白酶9(MMP-9)的血清含量及组织表达的相关性,探讨MMP-2和MMP-9与胃癌侵袭、转移的关系,收集2007年4月～2007年11月吉林大学第二医院普外科住院手术治疗的38例胃癌患者的癌组织和术前血清标本,运用免疫组织化学PV-9000通用型二步法和ELSIA法对胃癌患者组织及血清中MMP-2和MMP-9的含量表达进行检测,结果发现:MMP-2和MMP-9在胃癌组织中的阳性表达率分别为94.7%和86.8%,与淋巴结转移、肿瘤分期显著相关(P<0.05);胃癌患者血清中MMP-2水平与正常对照组比较无显著差异(P>0.05);胃癌患者血清中MMP-9的含量明显高于正常对照组,差异有显著性(P<0.05),且其含量与淋巴结转移、肿瘤分期显著相关(P<0.05)。可得出以下结论:MMP-2和MMP-9在胃癌组织中高表达,且与淋巴结转移、肿瘤分期显著相关;胃癌患者血清中MMP-2的含量与组织中MMP-2的表达没有相关性,血清中MMP-9的含量与组织中MMP-9的表达具有相关性,且与淋巴结转移、肿瘤分期显著相关;检测胃癌患者术前血清中MMP-9的含量有助于预测肿瘤的TNM分期、淋巴结是否发生转移,从而为制定合理的手术方案提供有效的信息。更多还原

【Abstract】 Gastric carcinoma is one of the most familiar malignant tumors. There is close affinity between its prognosis and the invasion and metastasis of cancer cells.Invasion and metastasis is character of malignant tumor,also is the main cause that leads patients to failure treatment and death.The invasion and metastasis is an extremely complex process controlled by polygene that needs many steps to develop, referring to reciprocity of broad tumor cells–host, cell- matrix.In the process of invasion and metastasis of cancer cells the significance of MMPs is accelerating cancer cells break through the histochemistry barriers through destroying the balance of degradation,then invade tissues around and transfer to tissues beyond.Both MMP-2 and MMP-9 are geltinases which are the most important ones of MMPs. With the effect of fusible medium or adhesion molecules tumor cells can change information with mesenchyma and cooperate with producing and regulating MMP-2 and MMP-9,which has the fatal significance in the mechanism study of tumor cells’invasion and metastasis.Object: To study the relativity of levels of MMP-2 and MMP-9 in serum and cancer tissues got from gastric carcinoma patients, dicuss relationship between them and clinical pathology parameters.Methods: 38 gastric carcinoma paraffin embed specimens resected by operation were collected from the second hospital of Jilin University from May to November in 2007.The expression of MMP-2 and MMP-9 in 38 resected specimens was analyed by PV-9000 polymer detection system for immunohistological staining. Immunohistochemistry pigmentation use the proportion of positive cells in all the cancer cells in every slice to estimate,choose randomly 5 fields to account under high power field,absolutely negative or positive rate<5% is (-),5%～25% is (+),26%～75% is (++),>75% is (+++). Enzyme-linked immunosorbent assay was used to detect the preoperative serum level of MMP-2 and MMP-9 in 38 patients with gastric cancer,compared with 20 healthy persons. Used the anthos 2010 to scan immediately after the reaction, elicited the concentration of every pore according to the OD value and calibration concentration. Used the statistic software CS-2000 to make statistics analysis.The result of immunohistochemistry use theχ2 proof-test;the result of ELISA expressed by mean( x)±SD(s) use the t proof-test.And P<0.05 has the statistics significance. Results: The positive expression of MMP-2 and MMP-9 in gastric carcinoma tissue specimens respectively was 94.7%(36/38)and 86.8%(33/38),there was significant relationship between the expression of MMP-2 and MMP-9 and the lymph node metastasis,TNM stage(P<0.05,respectively);the level of MMP-2 in serum of gastric carcinoma patients and control group respectively was 48.80±22.17ng/ml and 53.02±24.04 ng/ml,there was no significant difference between the gastric patients and the control group(P>0.05); the level of MMP-9 in serum of gastric carcinoma patients and control group respectively was 210.97±94.29 ng/ml and 60.36±25.74 ng/ml,there was significant difference between the gastric patients and the control group (P<0.05),also there was significant relationship between the expression of MMP-9 in serum and the lymph node metastasis,TNM stage(P<0.05,respectively).Discussion: The high expression of MMP-2 and MMP-9 in tissue and the high level of MMP-9 in serum in patients with gastric carcinoma was already approved by many academicians. Basically this became a verdict. And now the controversy is whether there is significant relationship of MMP-2 in serum between the gastric carcinoma patients and the control group. Through this investigation we elicited that the concentration of MMP-2 in serum in gastric carcinoma patients had no significant difference with the control group , the explanation as follows: 1.MMP-2 can be activated by fibroblast,so there is high expression in tissue;MMP-9 can be activated by fibrinoclase,so the level in serum is relatively high.2.Because MMP-2 mainly root in many connective tissue cells , MMP-9 mainly root in neutrophile granulocyte and macrophage.Under the normal condition,there is a small quantity of expression respectively of MMP-2 and MMP-9.And the results of immunohistochemistry told us that there was difference between MMP-2 and MMP-9 in the same gastric carcinoma tissues,more strong positive of MMP-2 and more positive of MMP-9.3.The methods of detecting is different,the different results due to the different reagent and laboratory environment.Especially the reagent, different binding site of antigen and antibody will lead to different results. 4.The content of MMP-2 in serum of gastric carcinoma patients which is detected by the way of ELSIA is gross.This way couldn’t detect simultaneously the active form and the zmogen form of MMP-2.So we couldn’t exclude the active form of MMP-2 has no significant difference with the control group,and the relativity with lymph node metastasis ,TNM stage. In all,this investigation of MMP-2 and MMP-9 offered credible theory gist for clinical effective and reasonable integrative Rx .At the same time,this hinted that people can control the invasion and metastasis of tumor through the interdiction of MMP-2 and MMP-9 to control and treat tumor.This also redound us to understand the molecular mechanism of metastasis of tumor one more step,but the particular mechanism still needs us investigate more thoroughly.Conclusion: There is high expression of MMP-2 and MMP-9 in gastric carcinoma tissues, and there was significant correlation with metastasis of lymph node and TNM stage. There was relativity of the expression of MMP-9 between the serum and the tissue.In the patients with gastric carcinoma,detecting the level of MMP-9 in serum before operation can prognosticate lymph node metastasis and TNM stage ,and provide useful information for establishing reasonable operation project. This is a good simple way without traumatic occlusion.更多还原