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AuthorPedersen, Shona
AuthorJensen, Katrine Papendick
AuthorHonoré, Bent
AuthorKristensen, Søren Risom
AuthorPedersen, Camilla Holm
AuthorSzejniuk, Weronika Maria
AuthorMaltesen, Raluca Georgiana
AuthorFalkmer, Ursula
Available date2022-01-24T09:48:10Z
Publication Date2022-12-01
Publication NameClinical Proteomics
Identifierhttp://dx.doi.org/10.1186/s12014-021-09339-5
CitationPedersen, S., Jensen, K.P., Honoré, B. et al. Circulating microvesicles and exosomes in small cell lung cancer by quantitative proteomics. Clin Proteom 19, 2 (2022). https://doi.org/10.1186/s12014-021-09339-5
ISSN15426416
URIhttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85122403342&origin=inward
URIhttp://hdl.handle.net/10576/25893
AbstractBackground: Early detection of small cell lung cancer (SCLC) crucially demands highly reliable markers. Growing evidence suggests that extracellular vesicles carry tumor cell-specific cargo suitable as protein markers in cancer. Quantitative proteomic profiling of circulating microvesicles and exosomes can be a high-throughput platform for discovery of novel molecular insights and putative markers. Hence, this study aimed to investigate proteome dynamics of plasma-derived microvesicles and exosomes in newly diagnosed SCLC patients to improve early detection. Methods: Plasma-derived microvesicles and exosomes from 24 healthy controls and 24 SCLC patients were isolated from plasma by either high-speed- or ultracentrifugation. Proteins derived from these extracellular vesicles were quantified using label-free mass spectrometry and statistical analysis was carried out aiming at identifying significantly altered protein expressions between SCLC patients and healthy controls. Furthermore, significantly expressed proteins were subjected to functional enrichment analysis to identify biological pathways implicated in SCLC pathogenesis. Results: Based on fold change (FC) ≥ 2 or ≤ 0.5 and AUC ≥ 0.70 (p < 0.05), we identified 10 common and 16 and 17 unique proteins for microvesicles and exosomes, respectively. Among these proteins, we found dysregulation of coagulation factor XIII A (Log2 FC = − 1.1, p = 0.0003, AUC = 0.82, 95% CI: 0.69–0.96) and complement factor H-related protein 4 (Log2 FC = 1.2, p = 0.0005, AUC = 0.82, 95% CI; 0.67–0.97) in SCLC patients compared to healthy individuals. Our data may indicate a novel tumor-suppressing role of blood coagulation and involvement of complement activation in SCLC pathogenesis. Conclusions: In comparing SCLC patients and healthy individuals, several differentially expressed proteins were identified. This is the first study showing that circulating extracellular vesicles may encompass specific proteins with potential diagnostic attributes for SCLC, thereby opening new opportunities as novel non-invasive markers.
Languageen
PublisherBMC
SubjectPotential diagnostic markers
Proteomics
Small cell lung cancer
Tumor-derived exosomes
Tumor-derived microvesicles
TitleCirculating microvesicles and exosomes in small cell lung cancer by quantitative proteomics
TypeArticle
Issue Number1
Volume Number19
dc.accessType Open Access


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