三阴性乳腺癌中 DNMT1表达与 ERα基因启动子甲基化的关系

摘要

Objective:To investigate the relationship between DNMT1 expression and ERαgene promoter methyla-tion and their clinical significance in triple -negative breast cancer(TNBC).Methods:The expression of DNMT1 protein was detected by immunohistochemical method,and the methylation level of ERαgene promoter was detected by methylation specific PCR method,in 126 cases of TNBC tissues.Results:In 126 cases of TNBC,the positive ex-pression rate of DNMT1 was 38.1%,and the ERαgene promoter methylation rate was 54.8%.DNMT1 expression level was significantly correlated with ERαgene promoter methylation(r =0.220,P =0.013).Compared with TNMⅠ -Ⅱ stage,ERαwas significantly increased in TNMⅢ -Ⅳ stage tissues(P =0.040),and the expression level of DNMT1 was significantly increased in the tissues with lymph node metastasis(P =0.043).ERαgene promoter methy-lation was significantly associated with shorter OS and DFS(P =0.020,P =0.036)in patients with TNBC.DNMT1 positive expression was significantly associated with shorter OS(P =0.034),and associated with a tendency of shorter DFS(P =0.054).Conclusion:DNMT1 is involved in the methylation of ERαgene in TNBC,and this event is associ-ated with the invasion and metastasis of breast cancer,the progress and adverse prognosis of TNBC.%目的：探讨三阴性乳腺癌中 DNMT1表达与 ERα基因启动子甲基化的关系，以及二者在三阴性乳腺癌中的临床意义。方法：采用免疫组化法检测了126例三阴性乳腺癌组织中 DNMT1蛋白的表达情况，同时采用甲基化特异性 PCR 法检测了 ERα基因启动子区甲基化水平。结果：126例三阴性乳腺癌中，DNMT1阳性表达率为38．1％，ERα基因启动子区甲基化率为54．8％，DNMT1表达水平与 ERα基因甲基化呈显著正相关（r ＝0．220，P ＝0．013）。与 TNMⅠ－Ⅱ期组织相比，在 TNMⅢ－Ⅳ期组织中 ERα基因甲基化显著增加（P＝0．040）；与无淋巴结转移的组织相比，发生淋巴结转移的组织中 DNMT1表达水平显著增加（P ＝0．043）。ERα基因启动子区甲基化与三阴性乳腺癌患者 OS 及 DFS 缩短显著相关（P ＝0．020，P ＝0．036）；DNMT1阳性表达可显著缩短患者 OS（P ＝0．034），同时可使患者 DFS 出现缩短趋势（P ＝0．054）。结论：三阴性乳腺癌中 DNMT1蛋白参与了 ERα基因甲基化，且该事件与三阴性乳腺癌的侵袭转移、病程进展及不良预后相关。