沉默信息调节因子2相关酶1在贲门癌中表达的意义及相互关系  

Expressions of SIRT 1,E-cadherin and MLH 1 in gastric cardia carcinoma and their relationship

作　　者：冯安宁[1] 樊祥山[1] 黄勤[1] 章宜芬[1] 叶庆[1] 吴鸿雁[1] 杨军[1] 张丽华[2] 

机构地区：[1]南京大学医学院附属鼓楼医院病理科,南京医学硕士210008 [2]东南大学附属中大医院病理科,南京210009

出　　处：《医学研究生学报》2011年第8期825-830,共6页Journal of Medical Postgraduates

基　　金：南京市医学科技发展重点项目(ZKX07011)

摘　　要：目的沉默信息调节因子2相关酶1(silent mating type information regulation 2 homolog 1,SIRT1)是活性依赖烟酰胺腺嘌呤二核苷酸(nicotinamide adenine dinucleotide,NAD)的去乙酰化酶,可能参与某些肿瘤的形成及进展,并对多种肿瘤相关基因的蛋白活性及基因沉默的调控中起重要作用。文中研究SIRT1及上皮钙黏蛋白(epithelial cadherin,E-cadherin)和错配修复蛋白1(Mutl homoolog 1,MLH1)在贲门癌中表达的临床病理学意义及相互关系。方法应用组织芯片技术和免疫组化EnVision二步法检测176例贲门癌患者癌组织中SIRT1、E-cadherin、MLH1蛋白的表达。结果 SIRT1表达阳性率与淋巴结转移数目及TNM分期呈正相关。E-cadherin和MLH1表达与淋巴结转移数目、TNM分期呈负相关。90例有随访资料病例中,SIRT1阳性患者3年生存率及平均生存时间显著低于SIRT1阴性患者。E-cadherin强阳性表达患者3年生存率及平均生存时间显著高于弱阳性表达患者,MLH1阳性表达患者的3年生存率及平均生存时间高于MHL1阴性患者,差异均有统计学意义。结论贲门癌中SIRT1阳性表达与肿瘤恶性程度正相关。E-cadherin表达程度及MLH1阳性表达与肿瘤恶性程度负相关,SIRT1可能通过E-cadherin、MLH1等抑癌基因的沉默作用促进贲门癌的形成,影响其恶性生物学行为。Objective SIRT 1 is a NAD+(nicotinmide nicotinamide adenine dinucleotide)-dependent deacetylase,which may be involved in the formation and progression of many types of carcinoma,and plays an important role in regulating protein function and gene silencing of certain tumor-related genes.The objective of the research is to investigate the clinicopathological significance of the expressions of SIRT 1,MLH 1 and E-cadherin in gastric cardia carcinoma and their relationship.Methods We detected the expressiond of SIRT 1,MLH 1 and E-cadherin proteins in the gastric cardia carcinoma tissues of 176 patients using the tissue microarray(TMA) technique and immunohistochemistry staining.Results The expression of SIRT 1 was positively correlated with lymph node metastasis(P=0.032) and TNM stages(P = 0.034),that of E-cadherin negatively with the histological differentiation(P=0.029),lymph node metastasis(P=0.000) and TNM stages(P=0.003),and that of MLH 1 showed no correlation with the clinicopathological features of gastric cardiac carcinoma,lymph node metastasis and TNM stages(P>0.05).The complete follow-up data of 90 cases exhibited that the three-year survival rate and and mean survival time were significantly lower and shorter in the SIRT 1-positive than in the SIRT 1-negative patients(P=0.024),higher and longer in the patients with a strong positive E-cadherin expression than in those with a weak one(P=0.001),and higher and longer,too,in those with a positive MLH 1expression than in those with a negative one(P = 0.045).Conclusion The expression of SIRT 1 in gastric cardia carcinoma is associated with lymph node metastasis,TNM stages and survival time,but it is not an independent prognostic factor,and that of E-cadherin is negatively correlated with the degree of malignancy.SIRT 1 may promote the formation of gastric cardia carcinoma and influence its biological behavior by silencing tumor suppressor genes,such as E-cadherin and MLH 1.

关 键 词：沉默信息调节因子2相关酶1 贲门癌 上皮钙黏蛋白 错配修复蛋白 生存期 预后 

分 类 号：R735[医药卫生—肿瘤]