Institute of Cell Biology and Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China.
Central Laboratory, Yangjiang People's Hospital, Yangjiang 529500, China.
Exp Biol Med (Maywood). 2021 Feb;246(4):387-399. doi: 10.1177/1535370220968058. Epub 2020 Nov 11.
Early diagnosis of active pulmonary tuberculosis (TB) is the key to controlling the disease. Host lipids are nutrient sources for the metabolism of . In this research work, we used ultra-high-performance liquid chromatography-tandem mass spectrometry to screen plasma lipids in TB patients, lung cancer patients, community-acquired pneumonia patients, and normal healthy controls. Principal component analysis, orthogonal partial least squares discriminant analysis, and K-means clustering algorithm analysis were used to identify lipids with differential abundance. A total of 22 differential lipids were filtered out among all subjects. The plasma phospholipid levels were decreased, while the cholesterol ester levels were increased in patients with TB. We speculate that the infection of may regulate the lipid metabolism of TB patients and may promote host-assisted bacterial degradation of phospholipids and accumulation of cholesterol esters. This may be related to the formation of lung cavities with caseous necrosis. The results of receiver operating characteristic curve analysis revealed four lipids such as phosphatidylcholine (PC, 12:0/22:2), PC (16:0/18:2), cholesteryl ester (20:3), and sphingomyelin (d18:0/18:1) as potential biomarkers for early diagnosis of TB. The diagnostic model was fitted by using logistic regression analysis and combining the above four lipids with a sensitivity of 92.9%, a specificity of 82.4%, and the area under the curve (AUC) value of 0.934 (95% CI 0.873 - 0.971). The machine learning method (10-fold cross-validation) demonstrated that the model had good accuracy (0.908 AUC, 85.3% sensitivity, and 85.9% specificity). The lipids identified in this study may serve as novel biomarkers in TB diagnosis. Our research may pave the foundation for understanding the pathogenesis of TB.
早期诊断活动性肺结核（TB）是控制该疾病的关键。宿主脂质是 代谢的营养来源。在这项研究工作中，我们使用超高效液相色谱-串联质谱法筛选了 TB 患者、肺癌患者、社区获得性肺炎患者和正常健康对照者的血浆脂质。主成分分析、正交偏最小二乘判别分析和 K-均值聚类算法分析用于识别具有差异丰度的脂质。在所有受试者中，共筛选出 22 个差异脂质。TB 患者的血浆磷脂水平降低，胆固醇酯水平升高。我们推测 可能会调节 TB 患者的脂质代谢，并可能促进宿主辅助细菌降解磷脂和胆固醇酯的积累。这可能与干酪样坏死性空洞的形成有关。受试者工作特征曲线分析的结果显示，四种脂质（PC（12：0/22：2）、PC（16：0/18：2）、胆固醇酯（20：3）和鞘磷脂（d18：0/18：1））作为 TB 早期诊断的潜在生物标志物。使用逻辑回归分析拟合诊断模型，并将上述四种脂质与敏感性为 92.9%、特异性为 82.4%、曲线下面积（AUC）值为 0.934（95%CI 0.873-0.971）相结合。机器学习方法（10 折交叉验证）表明该模型具有良好的准确性（AUC 为 0.908，敏感性为 85.3%，特异性为 85.9%）。本研究中鉴定的脂质可能成为 TB 诊断的新型生物标志物。我们的研究可能为理解 TB 的发病机制奠定基础。
