MALDI-TOF质谱在乳腺癌诊断及分型中的应用  

Application of MALDI-TOF mass spectrometry in diagnosis and classification of breast cancer

作　　者：许小雨 宋御繁 孙克娜 陈英剑 胡成进 XU Xiaoyu;SONG Yufan;SUN Kena;CHEN Yingjian;HU Chengjin(Department of Medical Laboratory,Weifang Medical University,Weifang 261053,Shandong;Clinical laboratory of the 960th Joint Logistic Support Force Hospital,Jinan 250031,Shandong,China)

机构地区：[1]潍坊医学院医学检验学院,山东潍坊261053 [2]联勤保障部队第九六〇医院检验科,济南250031

出　　处：《临床检验杂志》2021年第12期909-914,共6页Chinese Journal of Clinical Laboratory Science

摘　　要：目的应用基质辅助激光解吸电离飞行时间质谱(MALDI-TOF-MS)技术建立乳腺癌诊断预测模型,寻找乳腺癌血清中的差异蛋白质/多肽,并区分三阴性乳腺癌(TNBC)与非三阴性乳腺癌(NTNBC)。方法共纳入61例乳腺癌患者、60例乳腺纤维腺瘤患者及44例体检健康者。按照3∶1的比例随机分为训练组(乳腺癌患者45例,体检健康者33例)和验证组(乳腺癌患者16例,健康人对照11例)。采用弱阳离子交换磁珠(WCX-MB)提取血清蛋白质/肽,基质辅助激光解吸电离飞行时间质谱(MALDI-TOF-MS)技术检测并筛选出差异峰,构建诊断预测模型并初步验证。观察分析乳腺癌患者血清蛋白质谱分子变化。结果应用ClinProTools软件构建了乳腺癌组与健康组的诊断预测模型。遗传算法(GA)模型的特异性为90.9%,敏感性为93.8%,准确性为92.6%。对纤维腺瘤组和对照组、乳腺癌组和纤维腺瘤组以及TNBC组和NTNBC组分别进行聚类分析,发现有显著差异峰可将其准确区分:差异峰m/z 4220.9、5920.36在纤维腺瘤组中的峰强度明显高于对照组,但其在乳腺癌组中的峰强度明显低于纤维腺瘤组;差异峰m/z 4220.9、5920.36在TNBC组中的峰强度明显高于NTNBC组。结论应用MALDI-TOF-MS技术建立的乳腺癌诊断预测模型具有高敏感性、高特异性的特点,该技术可用于乳腺癌患者的鉴别诊断以及区分乳腺癌的基因分型。Objective To establish a diagnosis and prediction model of breast cancer by matrix-assisted laser desorption ionization time-of-flight mass spectrometry(MALDI-TOF-MS),to search for differential proteins/peptides in serum of breast cancer,and to distinguish triple negative breast cancer(TNBC)from non-triple negative breast cancer(NTNBC).Methods 61 breast cancer patients,60 breast fibroadenoma patients and 44 healthy subjects were included in the study.The patients were randomly divided into training group(45 cases of breast cancer,33 cases of healthy subjects)and verification group(16 cases of breast cancer,11 cases of healthy subjects)according to the ratio of 3∶1.After the serum protein/peptide was extracted by weak cation exchange magnetic beads(WCX-MB),matrix assisted laser desorption ionization time-of-flight mass spectrometry(MALDI-TOF-MS)was used to detect and screen the difference peaks,and the diagnostic prediction model was established and preliminatively verified.To observe and analyze the molecular changes of serum protein profile in patients with breast cancer.Results ClinProTools provided diagnostic prediction models for breast cancer group and healthy group.The specificity,sensitivity and accuracy of genetic algorithm(GA)model were 90.9%,93.8%and 92.6%respectively.Cluster analysis was conducted for fibroadenoma group and control group,breast cancer group and fibroadenoma group,and TNBC group and NTNBC group respectively,and significant difference peaks were found to be able to accurately distinguish them:The peak intensity of m/z 4220.9 and 5920.36 in fibroadenoma group was significantly higher than that in control group,but the peak intensity of m/z 4220.9 and 5920.36 in breast cancer group was significantly lower than that in fibroadenoma group.The peak intensity of m/z 4220.9 and 5920.36 in TNBC group was significantly higher than that in NTNBC group.Conclusion The diagnosis and prediction model of breast cancer established by MALDI-TOF-MS has the characteristics of high sensitivity and high sp

关 键 词：基质辅助激光解吸电离飞行时间质谱 诊断预测模型 血清 三阴性乳腺癌 乳腺癌 

分 类 号：R737.9[医药卫生—肿瘤] R446.9[医药卫生—临床医学]