质谱在乳腺癌血清蛋白组中的应用及其临床意义

Application of MALDI-TOF-MS for serum proteome profiling in breast carcinomas and its clinical significance

目的研究乳腺癌患者血清蛋白,筛选候选肿瘤标志物并建立诊断模型,初步探讨所建立的诊断模型在乳腺癌早期诊断中的临床意义。方法对48例乳腺浸润性导管癌患者和26例乳腺良性肿瘤患者与52名健康人血清,采用弱阳离子交换型(WCX)纳米磁珠联合基质辅助激光解析离子化飞行时间质谱,检测各血清标本获得蛋白指纹图谱;用Biomarker Wizard找出差异蛋白,再用Biomarker Patterns建立诊断模型;扩大样本量,通过盲法分析进一步验证诊断模型。结果初步筛选出6个差异蛋白峰,差异有统计学意义(P<0.01),建立由3164、3403 m/z两个差异蛋白峰组成的乳腺癌诊断模型,其敏感率为90.0%,特异性为93.3%;扩大样本盲法验证结果其敏感性为77.8%,特异性为90.9%;另外26例乳腺良性肿瘤患者中有21例可以检出。结论由两个差异表达蛋白及其特定组合构成的诊断模型可以区分乳腺浸润性导管癌、乳腺良性肿瘤患者与健康人。

OBJECTIVE To analyze the serum proteomic patterns in the breast cancer patients,build diagnostic models and evaluate its clinical significance.METHODS WCX magnetic bead and MALDI-TOF-MS were used to detect the serum proteome patterns of 48 patients with invasive breast carcinomas,26 patients with benign breast disease and 52 healthy women.Biomarker Wizard software was used to detect protein peaks significantly different between breast cancer and controls.The model was built by Biomarker Patterns which was further valuated by the large scale in blind test.RESULTS Six peaks were significantly different between invasive breast carcinomas and controls（P0.01）.A diagnostic pattern consisting of two differential protein peaks was established with 90.0%sensitivity and 93.3%specificity.A sensitivity of 77.8% and a specificity of 90.9%for the large scale in blind test were obtained.The diagnostic pattern also could discriminate benign breast disease patients from controls.CONCLUSION The diagnostic pattern combining 3164,3403 m/z two protein peaks can discriminate breast cancer from controls.