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目的分析特发性肺纤维化(IPF)患者支气管肺泡灌洗液(BALF)中蛋白质谱变化,寻找特异性蛋白标记物,评价这些标记物对IPF的诊断价值及临床应用前景。方法收集IPF患者及对照组BALF标本,应用表面增强激光解析/电离飞行时间质谱(SELDI-TOF-MS)技术筛选差异蛋白。通过非线性支持向量机方法建立诊断模型,并留一交叉验证法评估各模型的预测效果。结果 IPF患者BALF中筛选出8个表达有显著差异的蛋白质峰,其中检测效率最高的4个低表达蛋白质峰质荷比(m/z)分别为1947.634、1975.519、2488.535及4950.230。以这4个蛋白质峰组合建立诊断模型,其特异性和敏感性均为100%。结论应用SELDI-TOF-MS技术分析获得的低分子量蛋白质峰在诊断中具有较高的灵敏度和特异性,这些小分子可能在IPF发病中起重要作用。
Objective To analyze the changes of protein profiles in bronchoalveolar lavage fluid (BALF) in patients with idiopathic pulmonary fibrosis (IPF) and find specific protein markers to evaluate the diagnostic value and clinical application of these markers in IPF. Methods The BALF specimens of IPF patients and control group were collected and the differentially expressed proteins were screened by surface-enhanced laser desorption / ionization time-of-flight mass spectrometry (SELDI-TOF-MS). The diagnostic model is established by the method of nonlinear support vector machine, and a cross-validation method is adopted to evaluate the predictive effect of each model. Results Eight BALF proteins from IPF patients were screened for significant differences in protein peaks. Among them, the peak and mass-to-charge ratios (m / z) of the four low expression proteins were 1947.634,1975.519,2488.535 and 4950.230, respectively. The combination of these four protein peaks to establish a diagnostic model, the specificity and sensitivity were 100%. Conclusion The low molecular weight protein peaks obtained by SELDI-TOF-MS analysis have higher sensitivity and specificity in diagnosis. These small molecules may play an important role in the pathogenesis of IPF.