维吾尔族女性乳腺增生性病变与癌变组织中Notch1基因甲基化的差异比较

Comparison of differences of Notch1 gene methylation between hyperplastic lesions tissues and breast cancer tissues in Uyghur women

目的比较维吾尔族女性乳腺导管增生性病变和导管癌变组织中Notch1基因甲基化的差异情况。方法应用MALDITOF MS定位和定量检测Notch1基因在维吾尔族乳腺普通型导管增生(usual ductal hyperplasia,UDH)、非典型性导管增生(atypical ductal hyperplasia,ADH)、导管原位癌(ductal carcinoma in situ,DCIS)、浸润性导管癌(invasive ductal carcinoma,IDC)中甲基化率的变化,分析其与临床病理特征的关系,采用免疫组化法检测Notch1蛋白表达并分析其与甲基化的关系。结果Notch1基因在UDH、ADH、DCIS、IDC的甲基化率逐渐降低(P<0.05),13个Cp G位点中9个位点甲基化率明显下降(P<0.05),其低甲基化率伴随着低分化、淋巴结转移和TNM高分期(P<0.05),Notch1基因低甲基化率与Notch1蛋白表达呈负相关(P<0.05)。结论 Notch1蛋白表达和甲基化率在乳腺导管的不同增生性病变及乳腺癌变组织中存在一定的差异,其生物学意义有待进一步研究。

Purpose To compare the difference of Notchl methylation in the breast cancer and hyperplastic lesions tissue from Uyghur in Xinjiang. Methods The methylation level ofNotchl gene in Uyghur breast tissues including usual ductal hy- perplasia （ UDH）, atypical ductal hyperplasia （ ADH ）, ductal carcinoma in situ（ DCIS）, and invasive ductal carcinoma（IDC） were detected by MALDI-TOF-MS technique. The association of the methylation level with clinical pathological characteristics of patients was analyzed. The expression of Notchl protein was de- tected by immunohistochemistry. The relationship between the methylation status and expression was assay. Results The methylation rate of Notchl gene in UDH, ADH, DCIS, and IDC group was gradually decreased （ P 〈 0.05 ）. The 9 CpG sites methylation level of 13 CpG sites are statistically lower in cancer tissues （P 〈 0.05 ）. The hypomethylation are accompanied with low differentiation, lymph node metastasis and high stage of TNM （P 〈 0. 05）. The lower DNA methylation is negatively correlated with the expression of Notchl （P 〈 0. 05）. Conclusion There was a differences of the expression and methylation rate of Notchl between breast cancer and hyperplastic lesions tissue, and its biological significances needs to be further studied.