【摘要】 目的检测NOEY2基因在乳腺癌发生不同阶段的甲基化状态及其在乳腺浸润性导管癌(IDC)中的mRNA表达水平,探讨NOEY2基因启动子区异常甲基化与乳腺癌发生发展的关系。方法收集2010年1月—2012年1月手术切除乳腺的女性患者标本,其中IDC组46例,乳腺普通型导管增生(UDH)组30例,癌旁正常乳腺组织(NBT)组20例,乳腺原位导管癌(DCIS)组20例,乳腺非典型导管增生(ADH)组13例,采用甲基化特异性PCR(MSP)检测NOEY2基因的甲基化率及水平,分析其与临床病理参数的关系;采用实时定量PCR检测30例IDC中NOEY2基因的mRNA相对表达量,分析NOEY2基因甲基化对其mRNA表达的影响。结果 IDC组的完全甲基化率高于NBT及UDH组(P<0.01);NOEY2基因完全甲基化与乳腺癌患者的临床分期、组织学分级有关(P<0.05),而与年龄、肿瘤大小、ER、PR、HER2无相关性(P>0.05);完全甲基化的IDC标本NOEY2 mRNA表达量低于部分甲基化的IDC标本(P<0.05);IDC中NOEY2基因的甲基化水平与NOEY2基因mRNA表达量呈负相关(r=-0.659,P<0.05)。结论 NOEY2基因启动子区异常高甲基化及其导致的mRNA表达下调在乳腺癌发生发展过程中起重要作用。更多还原

【Abstract】 Objective To examine the methylation of NOEY2 gene in the process of breast cancer and mRNA expression in mammary infiltrating duct carcinoma( IDC),and to study the relationship between anormal methylation of NOEY2 genic promoter region and pathogenesy of breast cancer. Methods Samples from women undergoing mammary glands resection during January 2010 and January 2012 were collected,including 46 cases of IDC,30 cases of usual ductal hyperplasia( UDH),20 cases of normal breast tissue( NBT),20 cases of ductal carcinoma in situ( DCIS) and 13 cases of atypical ductal hyperplasia( ADH). The methylation rate and level of NOEY2 were detected using methylationspecific PCR( MSP),and the relationship between special methylation and indexes of clinical pathology was also analyzed; the opposite expressions of NOEY2 mRNA in 30 cases of IDC were detected using quantitative polymerase chain reaction,and the effect of NOEY2 gene of methylation on mRNA expression was also analyzed. Results The completemethylation rate in IDC group was higher than those in NBT and UDH groups( P < 0. 05); there were correlations between complete-methylation rate of NOEY2 gene and clinical stages and histological grades( P < 0. 05),while there were no correlations between complete-methylation rate and age,tumor size,ER,PR and HER2 in patients with breast cancer( P > 0. 05); expression of NOEY2 gene in complete-methylation IDC samples was lower than that in part-methylation IDC samples( P < 0. 05); level and NOEY2 mRNA expression in IDC samples was negatively correlated with mRNA expression( r =-0. 659,P < 0. 05). Conclusion Abnormal methylation of NOEY2 Cp G islandⅠ and induced low expression of NOEY2 mRNA may play an important role in the breast carcinogenesis and tumor progression.更多还原