Circulating microvesicles and exosomes in small cell lung cancer by quantitative proteomics

Shona Pedersen; Katrine Papendick Jensen; Bent Honoré; Søren Risom Kristensen; Camilla Holm Pedersen; Weronika Maria Szejniuk; Raluca Georgiana Maltesen; Ursula Falkmer

doi:10.1186/s12014-021-09339-5

Circulating microvesicles and exosomes in small cell lung cancer by quantitative proteomics

Clin Proteomics. 2022 Jan 7;19(1):2. doi: 10.1186/s12014-021-09339-5.

Authors

Shona Pedersen^#¹, Katrine Papendick Jensen^#^{2

3}, Bent Honoré^{2

4}, Søren Risom Kristensen^{2

3}, Camilla Holm Pedersen⁵, Weronika Maria Szejniuk^{2

6}, Raluca Georgiana Maltesen⁷, Ursula Falkmer^{2

6}

Affiliations

¹ Department of Basic Medical Sciences, College of Medicine, QU Health, Qatar University, 2713, Doha, Qatar. spedersen@qu.edu.qa.
² Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
³ Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark.
⁴ Department of Biomedicine, Aarhus University, Aarhus, Denmark.
⁵ Department of Health Science and Technology, Aalborg University, Aalborg, Denmark.
⁶ Department of Oncology, Aalborg University Hospital, Aalborg, Denmark.
⁷ Translational Radiation Biology and Oncology Laboratory, Centre for Cancer Research, Westmead Institute of Medical Research, Westmead, 2145, Australia.

^# Contributed equally.

Abstract

Background: 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.

Keywords: Potential diagnostic markers; Proteomics; Small cell lung cancer; Tumor-derived exosomes; Tumor-derived microvesicles.