Metabolomic Profiling of Large Extracellular Vesicles in Patients Suffering from Small Cell Lung Cancer

Background/Aim: Large extracellular vesicles (lEV) offer a unique window into the metabolism of their cells of orign and dysregulation of lipid metabolism has been described in patients with small cell lung cancer (SCLC). Therefore, metabolomic profiling of patients' lEVs may offer insight into cancer metabolism as well as new potential biomarkers for monitoring disease progression. Materials and Methods: lEVs were isolated by differential centrifugation from the peripheral blood of SCLC patients and healthy controls. Targeted mass spectrometry was used to analyze the lipid composition of lEVs. After identifying relevant metabolites, biomarker and pathway analysis were conducted. Results: SCLC patients exhibited a distinct metabolic profile compared to healthy controls. The metabolites TG(16:0:_38:3), TG(18:3_35:2), TG(16:0_40:7), Cer(d18:1/26:0), and CE(16:0) are not only able to discriminate between patients and control samples, but are also served as prognostic markers for survival. Patients with high concentrations of these metabolites showed significantly shorter survival times. Pathway analysis revealed alterations in 'sphingolipid metabolism', 'sphingolipid signaling pathway' and 'necroptosis'. Conclusion: Metabolic profiling of lEVs in SCLC patients is feasible and reveals a distinct metabolic profile. High concentrations of identified lipids are associated with poor prognosis.