MTSS1基因表达异常及杂合性缺失在晚期胃癌发展及转移中的作用  

Loss of heterozygosity and abnormal expression of MTSS1 in the progression and metastasis of advanced primary gastric carcinoma

作　　者：范理宏[1,2] 柳珂[1] 于观贞[1] 陈颖[3] 王喜[1] 潘军[1] 李萍[1] 王杰军[1] 

机构地区：[1]第二军医大学附属长征医院肿瘤科,上海200070 [2]上海交通大学附属第六人民医院肺内科,上海200233 [3]第二军医大学长海医院病理科,上海200433

出　　处：《肿瘤》2011年第3期255-260,共6页Tumor

摘　　要：目的:通过检测转移抑制因子1 (metastasis suppressor 1 ,MTSS1)基因在胃癌等组织中的表达,分析该基因在各组织中变化与胃癌预后的关系,并探讨该基因在胃癌发展及转移进程中变化的相关分子机制。方法:分别采用免疫组织化学法和RT-PCR法检测胃癌原发灶组织及其相应癌旁正常黏膜组织,淋巴结或其他转移灶组织中MTSS1的表达,并分析其与胃癌病理学参数的相关性。采用PCR-变性聚丙烯酰胺凝胶电泳银染法检测MTSS1阴性表达患者MTSS1基因位点上D8S1832、D8S2132、D8S1179和D8S14614等4个微卫星位点杂合性缺失(loss of heterozygosity, LOH)的情况。结果:MTSS1在胃癌原发灶组织中阳性表达率为33.9% (42/124),在胃癌淋巴结及其他转移灶中阳性表达率仅为16.3% (8/49)。MTSS1表达缺失与胃癌肿瘤的分化程度、浸润程度较深、发生淋巴结转移以及疾病分期晚等均明显相关。单因素与多因素分析均提示,MTSS1表达下降或缺失的胃癌患者预后较差。在MTSS1表达阴性的胃癌原发及转移组织中LOH发生率较高,总LOH率分别为46.2%和 69.2%。结论:MTSS1表达下降或缺失在胃癌的发生、发展过程中可能起着重要作用,基因可能与胃癌患者的预后密切相关。Objective：To determine the correlation of metastasis suppressor 1（MTSS1） gene with the prognosis of gastric cancer by detecting the expression level of MTSS1 in gastric cancer,and to explore its underlying molecular mechanism in the development and progression of gastric cancers.Methods：The expression levels of MTSS1 in the primary lesion,adjacent normal mucosa tissue,lymph node metastasis and other metastatic lesions from patients with gastric cancer were detected by using immunohistochemistry and RT-PCR,and the correlation of MTSS1 expression with the clinicopathological factors was evaluated.The loss of heterozygosity（LOH） of four microsatellite loci（D8S1832,D8S2132,D8S1179 and D8S1461） in MTSS1 gene in thirteen patients with negative-expression of MTSS1 was detected by using PCR-polyacrylamide gel electrophoresis-silver staining method.Results：The positive expression rates of MTSS1 were 33.9%（42/124） in the primary lesions and 16.3%（8/49） in the lymph node metastasis and other metastatic lesions.Loss expression of MTSS1 was significantly associated with the advanced T stage,lymph node metastasis,advanced disease stage,and the poor histological differentiation.Loss or down-regulation of MTSS1 expression was significantly correlated with the poor survival rate in both univariate and multivariate analysis.A higher frequency of allelic loss was observed in the primary（46.2%） or metastatic（69.2%） gastic cancer lesion with negative expression of MTSS1.Conclusion：The loss and decreased expression of MTSS1 may play an important role in the development and progression of gastric cancers,and MTSS1 gene may become a potential predictor for clinical outcome of patients with gastric cancer.

关 键 词：胃肿瘤 肿瘤抑制蛋白质类 免疫组织化学 预后 

分 类 号：R735.3[医药卫生—肿瘤]