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

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).

Delineating the role of extracellular vesicles in cancer metastasis: A comprehensive review

“…It is important to highlight the fact that each of these miRNA species has a role connected to cancer and has been linked to the progression of lung cancer. In addition, a handful of them, including recognized oncomirs miR-17, miR-19, miR-21, and miR-221, emerged in many miRNA signatures of lung cancer based on both the total serum/plasma and serum/plasma-derived EVs (148). Another group demonstrated that macrophage migration inhibitory factor, or MIF, was significantly expressed in EVs formed from pancreatic ductal adenocarcinomas (PDAC), and that blocking MIF inhibited the establishment of a pre-metastatic niche in the liver as well as metastasis.…”

Metabolomics of Extracellular Vesicles: A Future Promise of Multiple Clinical Applications

“…Significant differences in EVs and serum lipid profiles were also observed. 91 Accordingly, these researches have demonstrated the sensitivity of metabolic markers to clarify malignant cancer, especially for highly heterogeneous nodules when using low-dose computed tomography (CT). However, more information and tests are needed to promote the availability of the technology.…”

“… Diagnosis Late myocardial necrosis of atherosclerotic Adipose tissue C16:0 ceramide and their derivatives [ 87 ] Acute pancreatitis Plasma Eicosatrienoic acid (C20:3), thiamine triphosphate. 2-Acetylfuran, cis-Citral [ 68 ] Gestational hypertension Plasma SM, acetyl CoA, methionine, phenylalanine, tryptophan, carotenoids, tyrosine, arginine, leucine [ 88 ] ST elevation myocardial infarction Plasma Ceramides, dihydroceramides, and sphingomyelins [ 69 ] Lung cancer Pleural effusions Phenylalanine, leucine, PC 35:0 and SM 44:3 [ 91 ] Serum Ceramides, PC and polyunsaturated acyl chains [ 92 ] Prostate cancer Urinary PS 18:1/18:1 and lactosylceramide (d18:1/16:0) [ 93 ] Benign prostate hyperplasia Urinary PC, PE, SM [ 31 ] Bipolar disorder Serum lysoPE 18: 0, lysoPE 14: 0, lysoPC 18: 0, and lysoPC 20: 1 [ 73 ] Schizophrenia Depressive disorder Chromochromic leukogystrophy …”

Emerging Roles of Exosomes in Cancer for Possible Clinical Use

“…The research articles of this Special Issue extend the knowledge about EVs for a broad range of cancer subtypes, such as glioblastoma [ 13 ], synovial sarcoma [ 14 ], pancreatic cancer [ 15 ], ovarian cancer [ 16 ], lung cancer [ 17 ], esophageal squamous cell carcinoma [ 18 ] and breast cancer [ 19 ].…”

“…Smolarz et al compared lipid profiles of serum-derived small EVs from participants of a prospective lung cancer screening study with three groups of participants: without lung lesions, with benign lung nodules, and with screening-detected lung cancer [ 17 ]. Differences identified between groups were only of limited power with possible applicability as biomarker in the early detection of lung cancer.…”