The Lipid Composition of Serum-Derived Small Extracellular Vesicles in Participants of a Lung Cancer Screening Study

SIMPLE SUMMARY: Molecular components of extracellular vesicles present in serum are potential biomarkers of lung cancer, however, none of them have been validated in the context of an actual early detection of lung cancer. Here, we compared the lipid profiles of vesicles obtained from participants in a lung cancer screening study, including patients with screening-detected cancer and individuals with benign pulmonary nodules or without pathological changes. A few lipids whose levels were different between compared groups were detected, including ceramide Cer(42:1) upregulated in vesicles from cancer patients. Furthermore, a high heterogeneity of lipid profiles of extracellular vesicles was observed, which impaired the performance of classification models based on specific compounds. ABSTRACT: Molecular components of exosomes and other classes of small extracellular vesicles (sEV) present in human biofluids are potential biomarkers with possible applicability in the early detection of lung cancer. Here, we compared the lipid profiles of serum-derived sEV from three groups of lung cancer screening participants: individuals without pulmonary alterations, individuals with benign lung nodules, and patients with screening-detected lung cancer (81 individuals in each group). Extracellular vesicles and particles were purified from serum by size-exclusion chromatography, and a fraction enriched in sEV and depleted of low-density lipoproteins (LDLs) was selected (similar sized vesicles was observed in all groups: 70–100 nm). The targeted mass-spectrometry-based approach enabled the detection of 352 lipids, including 201 compounds used in quantitative analyses. A few compounds, exemplified by Cer(42:1), i.e., a ceramide whose increased plasma/serum level was reported in different pathological conditions, were upregulated in vesicles from cancer patients. On the other hand, the contribution of phosphatidylcholines with poly-unsaturated acyl chains was reduced in vesicles from lung cancer patients. Cancer-related features detected in serum-derived sEV were different than those of the corresponding whole serum. A high heterogeneity of lipid profiles of sEV was observed, which markedly impaired the performance of classification models based on specific compounds (the three-state classifiers showed an average AUC = 0.65 and 0.58 in the training and test subsets, respectively).