Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, China.
The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
J Clin Lab Anal. 2021 Apr;35(4):e23706. doi: 10.1002/jcla.23706. Epub 2021 Feb 2.
Tuberculous pleural effusions (TBPEs) and malignant pleural effusions (MPEs) are two of the most common and severe forms of exudative effusions. Clinical differentiation is challenging; however, metabolomics is a collection of powerful tools currently being used to screen for disease-specific biomarkers.
17 TBPE and 17 MPE patients were enrolled according to the inclusion criteria. The normalization gas chromatography-mass spectrometry (GC-MS) data were imported into the SIMCA-P + 14.1 software for multivariate analysis. The principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA) were used to analyze the data, and the top 50 metabolites of variable importance projection (VIP) were obtained. Metabolites were qualitatively analyzed using the National Institute of Standards and Technology (NIST) databases. Pathway analysis was performed by MetaboAnalyst 4.0. The detection of biochemical indexes such as urea and free fatty acids in these pleural effusions was also verified, and significant differences were found between these two groups.
1319 metabolites were screened by non-targeted metabonomics of GC-MS. 9 small molecules (urea, L-5-oxoproline, L-valine, DL-ornithine, glycine, L-cystine, citric acid, stearic acid, and oleamide) were found to be significantly different (p < 0.05 for all). In OPLS-DA, 9 variables were considered significant for biological interpretation (VIP≥1). However, after the ROC curve was performed, it was found that the metabolites with better diagnostic value were stearic acid, L-cystine, citric acid, free fatty acid, and creatinine (AUC > 0.8), with good sensitivity and specificity.
Stearic acid, L-cystine, and citric acid may be potential biomarkers, which can be used to distinguish between the TBPE and the MPE.
结核性胸腔积液（TBPE）和恶性胸腔积液（MPE）是两种最常见和最严重的渗出性胸腔积液形式。临床鉴别具有挑战性；然而，代谢组学是一组目前用于筛选疾病特异性生物标志物的强大工具。
根据纳入标准纳入 17 例 TBPE 和 17 例 MPE 患者。将归一化气相色谱-质谱（GC-MS）数据导入 SIMCA-P+14.1 软件进行多变量分析。采用主成分分析（PCA）和正交偏最小二乘判别分析（OPLS-DA）对数据进行分析，获得前 50 个变量重要性投影（VIP）代谢物。使用国家标准与技术研究所（NIST）数据库对代谢物进行定性分析。通过 MetaboAnalyst 4.0 进行代谢途径分析。还验证了这些胸腔积液中生化指标如尿素和游离脂肪酸的检测，发现两组之间存在显著差异。
通过 GC-MS 的非靶向代谢组学筛选出 1319 种代谢物。发现 9 种小分子（尿素、L-5-氧脯氨酸、L-缬氨酸、DL-鸟氨酸、甘氨酸、L-胱氨酸、柠檬酸、硬脂酸和油酰胺）差异显著（p<0.05 均）。在 OPLS-DA 中，认为有 9 个变量对生物学解释具有重要意义（VIP≥1）。然而，在进行 ROC 曲线后，发现具有更好诊断价值的代谢物是硬脂酸、L-胱氨酸、柠檬酸、游离脂肪酸和肌酐（AUC>0.8），具有良好的敏感性和特异性。
硬脂酸、L-胱氨酸和柠檬酸可能是潜在的生物标志物，可用于区分 TBPE 和 MPE。
