GBX2启动子区域甲基化位点对乳腺良恶性结节鉴别诊断的临床价值研究  

Differential diagnostic value of differential methylation sites in DNA isolated from peripheral blood mononuclear cells for benign and malignant breast nodules

作　　者：张莹 谢艳 李培龙 杜鲁涛 王传新 ZHANG Ying;XIE Yan;LI Pei-long;DU Lu-tao;WANG Chuan-xin(Department of Clinical Laboratory,The Second Hospital of Shandong University,Jinan 250033,China;Tumor Marker Detection Engineering Laboratory of Shandong Province,Jinan 250033,China)

机构地区：[1]山东大学第二医院检验医学中心,山东济南250033 [2]山东省肿瘤标志物检测工程实验室,山东济南250033

出　　处：《中国现代普通外科进展》2022年第4期264-269,共6页Chinese Journal of Current Advances in General Surgery

基　　金：国家自然科学基金项目(82002229)。

摘　　要：目的:探讨基于外周血单个核细胞(PBMCs)的DNA差异甲基化修饰位点在乳腺良恶性结节中的鉴别诊断价值。方法:采用Infinium MethylationEPIC BeadChip对25例乳腺癌(BCa)患者以及20例乳腺良性结节患者(发现队列)PBMCs的DNA差异甲基化位点(DMPs)进行分析,基于特定筛选原则获得DMPs,进一步提取42例BCa患者和42例乳腺良性结节患者(验证队列)PBMCs的DNA并通过目标区域甲基化测序比较BCa组和良性对照组之间DMPs的表达水平。利用受试者工作特征曲线(ROC)评估上述DMPs的诊断价值。结果:发现队列的BCa患者和乳腺良性疾病患者的PBMCs差异DNA甲基化图谱具有显著差异,通过筛选得到5个DMPs(cg05391486,cg05492964,cg13848429,cg14220764,cg21426003)。在验证队列中,BCa组PBMCs的cg21426003的表达水平显著高于良性对照组(P<0.0001)。ROC曲线下面积(AUC)为0.807(95%CI:0.707,0.885),优于CA15-3。结论:cg21426003在BCa患者PBMCs中甲基化水平较乳腺良性结节患者明显升高,可以作为乳腺良恶性结节鉴别诊断的新型分子标志物。Objective:To investigate the differential diagnosis value of differential methylation sites in DNA isolated from peripheral blood mononuclear cells(PBMCs)for breast malignant and benign nodules.Methods:The Infinium MethylationEPIC BeadChip was used to analyze the differential methylation sites(DMPs)of PBMCs from 25 breast cancer(BCa)patients and 20 patients with benign breast nodules,and DMPs were obtained.DNA from PBMCs of 42 BCa patients and 42 patients with benign breast nodules was extracted and the methylation levels of DMPs between the BCa group and the benign lesion group was evaluated by target region methylation sequencing.The diagnostic value of DMPs was assessed by receiver operating characteristic(ROC)curves and compared with traditional markers.Results:Altas of DMPs in PBMCs in patients with BCa and breast benign diseases showed significant differences and 5 DMPs(cg05391486,cf05492964,cg13848429,cg14220764,cg21426003)were obtained.In the validation stage,the expression of cg21426003 in PBMCs of BCa group was significantly higher than that of benign lesion group(P<0.0001).The area under the ROC curve(AUC)was 0.807(95%CI:0.707~0.885),which was prior to CA15-3.Conclusion:cg21426003 in PBMCs of BCa patients is significantly hypermethylated in BCa patients,and it can be used as a novel and promising molecular marker for the differential diagnosis of breast benign and malignant nodules.

关 键 词：乳腺肿瘤 乳腺良性结节 外周血单个核细胞PBMCs DNA甲基化 鉴别诊断 

分 类 号：R737.9[医药卫生—肿瘤]