CAJ | 학술논문

目的：本研究通过检测DNA甲基转移酶（DNM T ）1在散发性乳腺癌中的表达，分析DNM T1与乳腺癌易感基因（BRCA）1蛋白表达及基因启动子甲基化状态的相关性，以探讨DNMT1在散发性乳腺癌中的临床意义。方法应用免疫组织化学法检测182例散发性乳腺癌与30例乳腺纤维腺瘤组织中DNM T1蛋白的表达水平，应用甲基特异化聚合酶链反应（PCR）检测97例散发性乳腺癌组织中BRCA1基因启动子区甲基化状态，采用χ2检验、Fisher确切概率法、Spearman等级相关进行统计学分析。结果与乳腺纤维腺瘤相比，乳腺癌组织中DNM T1蛋白表达水平均显著增高（ P ＝0．013）；在发生淋巴结转移的组织中DNM T1蛋白表达量增多（ P ＝0．014）；用甲基特异化PCR法检测97例乳腺癌标本中BRCA1蛋白基因启动子区甲基化率为19．6％；DNM T1蛋白的表达与BRCA1基因启动子区甲基化呈正相关（ r ＝ 0．349，P ＜0．01）；BRCA1和DNM T1阳性表达有降低患者总体生存期（OS）（ P ＝0．059，P ＝0．041）和无病生存期（DFS）（ P ＝0．054，P ＝0．026）的趋势。结论乳腺癌中DNM T1蛋白高表达与肿瘤侵袭转移相关，并且可能存在DNM T1催化BRCA1基因甲基化，从而下调BRCA1蛋白表达，进而导致乳腺癌患者预后不良的机制，提示抑制DNM T1可能利于乳腺癌的治疗。
목적：본연구통과검측DNA갑기전이매（DNM T ）1재산발성유선암중적표체，분석DNM T1여유선암역감기인（BRCA）1단백표체급기인계동자갑기화상태적상관성，이탐토DNMT1재산발성유선암중적림상의의。방법응용면역조직화학법검측182례산발성유선암여30례유선섬유선류조직중DNM T1단백적표체수평，응용갑기특이화취합매련반응（PCR）검측97례산발성유선암조직중BRCA1기인계동자구갑기화상태，채용χ2검험、Fisher학절개솔법、Spearman등급상관진행통계학분석。결과여유선섬유선류상비，유선암조직중DNM T1단백표체수평균현저증고（ P ＝0．013）；재발생림파결전이적조직중DNM T1단백표체량증다（ P ＝0．014）；용갑기특이화PCR법검측97례유선암표본중BRCA1단백기인계동자구갑기화솔위19．6％；DNM T1단백적표체여BRCA1기인계동자구갑기화정정상관（ r ＝ 0．349，P ＜0．01）；BRCA1화DNM T1양성표체유강저환자총체생존기（OS）（ P ＝0．059，P ＝0．041）화무병생존기（DFS）（ P ＝0．054，P ＝0．026）적추세。결론유선암중DNM T1단백고표체여종류침습전이상관，병차가능존재DNM T1최화BRCA1기인갑기화，종이하조BRCA1단백표체，진이도치유선암환자예후불량적궤제，제시억제DNM T1가능리우유선암적치료。
Objective To discuss the expression of DNA methyltransferases (DNM T )1 and the correlation between DNM T1 and BRCA1 protein expression ,BRCA1 gene promoter methylation in sporadic breast cancer . Methods By immunohistochemical staining ,the expression of DNMT1 protein was detected in 182 cases of spo‐radic breast cancer and 30 cases of breast fibroadenoma tissue .Using MSP‐PCR ,BRCA1 gene promoter methyla‐tion status was detected in 97 cases of sporadic breast cancer .The results were analyzed with χ2 test ,Fisher exact test and Spearman rank correlation .Results Compared with breast fibroadenoma ,the level of DNMT1 protein ex‐pression in breast cancer tissues is significantly increased ( P =0 .013);DNM T1 protein have a higher expression in the tissues with lymph node metastasis ( P=0 .014).The expression of DNMT1 protein and BRCA1 gene pro‐moter methylation had a significant positive correlation ( r =0 .349 ,P <0 .01);the expression of DNMT1 can shorten the patients′s OS and DFS .Conclusion The higher expression level of DNMT1 protein in sporadic breast cancer was associated with invasion and metastasis of tumor ;and DNM TI might catalyze the methylation of BRCA1 ,thus down‐regulated the expression of BRCA1 protein ,which might be the mechanism leading to poor prognosis in patients with breast carcinoma .It is prompted that the inhibition of DNM T 1 may be beneficial to the treatment of breast cancer.