【作者】 孙承宇；

【导师】 王强；

【作者基本信息】 中国医科大学 ， 外科学， 2007， 硕士

【摘要】 目的研究MMP-2(matrix metalloproteinase 2)、MMP-9(matrix metalloproteinase 9)和PPAR_γ(peroxisome proliferators activated receptorγ)在人体胃癌组织中的表达及其与胃癌生物学行为的关系，了解MMP-2、MMP-9和PPAR_γ与胃癌的侵袭及淋巴结转移的关系，寻找预测胃癌淋巴结转移的分子标志物，并为MMP及PPARs靶向个体化治疗提供证据。探讨正常胃粘膜、胃癌组织中MMP-2、MMP-9及PPARs的表达及其临床意义。方法收集75例有完整随访资料的胃腺癌手术切除标本及15例非肿瘤性胃粘膜组织标本，经溶脂法获取每例标本的全部淋巴结，所有淋巴结均进行连续间断切片、常规HE染色和CK18+EMA免疫组织化学染色，以确定有无淋巴结转移及微转移；N分期按照UICC／AJCC标准，即No：无淋巴结转移，N1：1-6个淋巴结转移，N2：7-15个淋巴结转移，N3：15个以上淋巴结转移。用免疫组织化学方法检测MMP-2、MMP-9及PPAR_γ在人体胃癌组织中的表达。全部数据经SAS8.1及SPSS13.0统计学软件处理。胃癌MMP-2、MMP-9和PPAR_γ的表达与有无淋巴结转移之间的差异用χ~2检验，P值＜0.05为有统计学意义。结果1、75例胃腺癌组织中，以MMP-2、MMP-9和PPAR_γ为一抗进行免疫组织化学染色后，可分析病例分别为75例、75例和75例。组织可利用率为100％。2、PPAR_γ与MMP-2、MMP-9的阳性表达率与胃癌的浸润深度、淋巴转移、临床分期呈正相关(P＜0.05)，随肿瘤浸润深度的加深、淋巴转移的产生、临床分期的提高而明显增高；与肿瘤的病理分化程度呈负相关(P＜0.05)，其阳性表达率随着肿瘤病理分化程度的降低而增高。3、Spearman等级相关分析显示，PPAR_γ与MMP-2、MMP-9表达呈负相关(r=-0.336、-0.401，P＜0.05)。结论1、胃癌组织中PPAR_γ与MMP-2、MMP-9呈现异常表达。2、胃癌组织中PPAR_γ与MMP-2、MMP-9的阳性率与肿瘤淋巴转移、临床分期、肿瘤病理分化程度密切相关，提示它们在胃癌的发生发展和浸润转移过程中有抑制或促进作用。3、胃癌组织中PPAR_γ与MMP-2、MMP-9的表达呈负相关，提示其在胃癌的发生发展以及浸润转移中存在着相互制约的作用。4、PPAR_γ与MMP-2、MMP-9各自都可以成为胃癌诊断和预后判断的指标。更多还原

【Abstract】 ObjectiveTo study the expression of MMP-2 (matrix metalloproteinase 2)、MMP-9 (matrix metalloproteinase 9) and PPARγ(peroxisomeproliferators activated receptorγ) in gastric adenocarcinoma and search predicting markers for lymph node metastasis in gastric adenocarcinoma. To investigate the relationship among MMP-2、MMP-9 and PPARγin the development of gastric carcinoma.MethodsTumor specimens were collected from 75 gastric adenocarcinoma cases and 20 cases non-tumor gastric tissue in which lymph nodes were also checked.All tumor specimens were consecutively cut into serial sections and examined by microscope. Total number of metastatic lymph nodes was counted. And staging was conducted according to the Classification of UICC/AJCC standard. N0:no lymph node metastasis, N1:1-6 lymph nodesmetastasis, N2:7-15 lymph nodes metastasis, N3:＞15 lymph nodes metastasis. The expression of MMP-2、MMP-9 and PPARγwas detected on the section of tissue microarray by immunohistochemistry.All data were processed using SAS 8.1 and SPSS 13.0 software. The difference of the expression of MMP-2、MMP-9 and PPARγin gastric adenocarcinoma with or without lymph node metastasis was processed usingχ~2-test, and P＜0.05 was considered statistical significance.Results 1、After using immunohistochemistry stain, MMP-2、MMP-9 and PPARγ, there were 75 cases left. The usable rate was 100％.2、The positive MMP-2、MMP-9 and PPARγexpression rate has positive correlation with infiltrated depth、lymphatic metastasis、clinical stage of gastric cancer (P＜0.05), and with deepening of the tumorous infiltrated depth, generating lymphatic metastasis, happening of far distance metastasis and increasing of clinical stage, positive MMP-2、MMP-9 and PPARγexpression rate rises obviously. Positive MMP-2、MMP-9 and PPARγexpression rate is negatively related with pathological differentiated degree of tumor (P＜0.05);it rises when pathological differentiated degree of tumor decreases.3、The expression of PPARγwas negative related to that of MMP-2, MMP-9 protein (r=-0.336、-0.401, P＜0.05).Conclusions1、Expression of PPARγand MMP-2、MMP-9 is abnormal in the gastric cancerous tissue.2、The close relationship between positive expression rate of PPARγ、MMP-2、MMP-9 in the gastric cancerous tissue and tumorous lymphatic metastasis、clinicalstage、pathological differentiated degree shows that they have suppressed or promotive effect in the development and infiltrating metastasis of gastric carcinoma.3、Negative correlation between PPARγand MMP-2、MMP-9 expression displays that they restrict each other in the process of gastric caicinoma happening、growth、infliltration and metastasis.4、PPARγand MMP-2、MMP-9 could be three markers to the diagnose and predict the prognosis of gastric cancer.更多还原