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

摘要

目的 沉默信息调节因子2相关酶l( silent mating type information regulation 2 homolog 1,SIRT 1)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 cad-herin,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、MLH 1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MLH 1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,MLH 1阳性表达患者的3年生存率及平均生存时间高于MHLI阴性患者,差异均有统计学意义. 结论 贲门癌中SIRT 1阳性表达与肿瘤恶性程度正相关.E-cadherin表达程度及MLH 1阳性表达与肿瘤恶性程度负相关,SIRT 1可能通过E-cadherin、MLH 1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 SIRT1 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 SIRT1, MLH1 and E-cadherin in gastric cardia carcinoma and their relationship. Methods We detected the ex-pressiond 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 SIRT1-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 1 expression than in those with a negative one (P = 0.045). Conclusion The expression of SIRT 1 in gas-tric 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. SIRT1 may promote the formation of gastric cardia carcinoma and influence its biological behavior by silencing tumor suppressor genes, such as E-cadherin and MLH1.