维吾尔族乳腺癌患者JAG1基因甲基化的临床意义

Clinical Signifi cance of JAG1 Gene Methylation in Uygur Breast Cancer Patients

目的探讨JAG1甲基化在维吾尔族乳腺癌变和进展过程中的临床意义。方法 MALDI-TOF MS法检测JAG1基因在15例乳腺普通型导管增生(usual ductal hyperplasia,UDH)、15例非典型性导管增生(atypical ductal hyperplasia,ADH)、15例导管原位癌(ductal carcinoma in situ,DCIS)和50例浸润性导管癌(invasive ductal carcinoma,IDC)组织中的甲基化率,免疫组织化学法检测蛋白表达,分析甲基化与蛋白表达的相关性。结果 JAG1基因在乳腺癌变过程组织中的甲基化率逐渐降低,以Cp G_11.12、Cp G_14.15、Cp G_18.19最显著(P<0.05),Cp G_1在低分化组明显降低(P<0.05),Cp G_8.9.10在淋巴结转移组明显降低(P<0.05),而Cp G_16.17在Ⅲ期中显著升高(P<0.05),Cp G_13、Cp G_26在ER、PR和HER2表达间差异有统计学意义(P<0.05),JAG1基因甲基化与蛋白表达显著负相关(r=-0.6 7 4 P<0.001)。结论JAG1基因CpG位点的不同甲基化水平在乳腺癌变进展中可能发挥不同作用。JAG1甲基化是蛋白表达的调控机制之一。

Objective To explore the clinical signifi cance of JAG1 gene methylation in the occurrence and progression of breast cancer in Uygur. Methods The methylation levels of JAG1 gene in 15 cases of usual ductal hyperplasia（UDH）, 15 cases of atypical ductal hyperplasia（ADH）, 15 cases of ductal carcinoma in situ（DCIS） and 50 cases of invasive ductal carcinoma（IDC） from women breast tissues were detected using MALDI-TOF MS method. Immunohistochemistry was used to detect JAG1 protein expression, and further the protein expression was associated with methylation in four groups of breast tissues. Results The overall methylation levels of JAG1 gene in different stages tissues of breast carcinogenic process were gradually decreased. The hypomethylation levels of JAG1 gene were most obvious in Cp G11.12, Cp G14.15, and Cp G18.19 sites（P〈0.05）. The level of Cp G1 methylation in low differentiation group was obviously reduced（P〈0.05） and low methylation rate of Cp G8.9.10 occurred in lymph node metastasis groups（P〈0.05）. However, the methylation level of Cp G16.17 was markedly increased in clinical Ⅲ stage（P〈0.05）. There was statistical significance between Cp G13, Cp G26 methylation levels and ER, PR, HER2 expression（P〈0.05）. JAG1 methylation rate and protein expression showed a negative correlation relationship（r=-0.674, P〈0.001）. Conclusion Different methylation levels of Cp G sites in JAG1 gene may play a distinct role in the progression of breast cancer. JAG1 methylation may be one mechanism of its protein expression.