非小细胞肺癌脑转移脑脊液蛋白质谱诊断模型的建立及其应用

Establishment of diagnostic model of cerebrospinal protein fingerprint pattern for brain metastases from non-small cell lung cancer and its clinical application

目的:分析非小细胞肺癌(non-smallcell lung cancer,NSCLC)脑转移患者脑脊液的蛋白质谱,建立NSCLC脑转移的蛋白质谱诊断模型。方法:采用表面增强激光解吸电离飞行时间质谱技术(surface-enhanced la-ser desorption/ionization ti me of flight massspectrometry,SELDI-TOF-MS)对29例脑转移NSCLC、23例非肿瘤和10例无脑转移NSCLC患者的脑脊液进行蛋白质谱分析,Biomarker Wizard软件统计分析3组样本的蛋白质峰,Biomarker Patterns软件的决策树模型进行差异蛋白峰的比较和判别,建立分类决策树诊断模型,评价其诊断和应用价值。结果:脑转移组和非肿瘤组之间有8个蛋白质峰表达差异有统计学意义,其中m/z6634.73蛋白质峰可把2组样本分开,灵敏度为89.66%(26/29),特异度为86.96%(20/23)。进一步行交叉验证结果显示其灵敏度为80.00%(8/10),特异度为70.00%(7/10)。脑转移组与无脑转移组有5个蛋白质峰表达差异有统计学意义,运用m/z8698.00、1215.32和1245.70蛋白质峰将2组样本分开,灵敏度和特异度均为100.00%(29/29)。结论:采用SELDI技术可以发现3组患者的脑脊液蛋白质峰表达差异有统计学意义,利用这些差异蛋白质建立的蛋白质谱分类决策树状诊断模型具有较高的灵敏性、特异性和准确率。

OBJECTIVE：To distinguish the protein expression profiling in cerebrospinal fluid（CSF）of non-small-cell lung cancer（NSCLC）patients with brain metastases,non-tumor patients and early stage NSCLC patients without brain metastases,and establish the diagnostic model of protein fingerprint pattern for brain metastases.METHODS：Samples mentioned above（29,23 and 10 cases,respectively）were collected and analyzed for protein expression using surface enhanced laser desorption/ionization-time of flight-mass spectrometry（SELDI-TOF-MS）.The obtained data were analyzed by Biomarker Wizard software,generation of tree analysis patterns were performed by Biomarker Patterns software decision-tree model.The diagnostic model was tested to evaluate its clinical application.RESULTS：There were 8 protein peaks differentially expressed between patients with brain metastases and non-tumor patients.With one protein peak（m/z 6 634.73）,these two samples could be discriminated from each other with sensitivity of 89.66%（26/29）and specificity of 86.96%（20/23）.The diagnostic model was further tested with cross validation,the sensitivity and specificity were 80.00%（8/10）and 70.00%（7/10）,respectively.There were 5 protein peaks differentially expressed between patients with and without brain metastases.Combination of 3 protein peaks（m/z 8 698.00,1 215.32 and 1 245.70）could discriminate these two samples with both sensitivity and specificity of 100.00%（29/29）.CONCLUSIONS：With SELDI technology remarkably differential CSF protein peaks are detected between these 3 groups of samples.The established diagnostic model of CSF protein fingerprint pattern provides high sensitivity,specificity and accuracy.