Metabolic and lipidomic characterization of malignant pleural effusion in human lung cancer

Malignant pleural effusion (MPE) is an important hallmark for late-stage lung cancer with metastasis. Current clinical diagnosis methods require tedious work to distinguish MPE from benign pleural effusion (BPE). The objective of this study was to characterize the metabolic signatures in MPE of lung cancer, and identify potential metabolite biomarkers for diagnosis of MPE. MPE from lung cancer (n = 46) and BPE from tuberculosis patients (n = 32) were investigated by liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based global metabolomic and lipidomic profiling. Multivariate partial least-square discriminative analysis models exhibited distinct metabolic profiles between MPE and BPE. A total of 25 ether lipids, including phosphatidylcholines (PC), lysophosphatidylcholines (LPC) and phosphatidylethanolamines (PE), were observed to be significantly downregulated in MPE with excellent diagnostic potential. Plasmalogen PC(40:3p) showed highest AUC value of 0.953 in receiver operating characteristic (ROC) model. Oxidized polyunsaturated fatty acids (PUFA) were upregulated in MPE. The obtained results implied a high oxidative stress and peroxisome disorder in lung cancer patients. Combined metabolomic and lipidomic profiling have discovered potential biomarkers in MPE with excellent clinical diagnostic capability. Dysregulated ether lipids and oxidized PUFAs have implied an aberrant redox metabolism, which provides novel insights into the pathology of MPE in lung cancer.