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

微泡 蛋白质组学 蛋白质组 外体 微泡 细胞外小泡 定量蛋白质组学 胞外囊泡 血液蛋白质类 生物 癌症研究 医学 小RNA 生物信息学 细胞生物学 内科学 生物化学 基因
作者
Shona Pedersen,Katrine Papendick Jensen,Bent Honoré,Søren Risom Kristensen,Camilla Holm Pedersen,Weronika Maria Szejniuk,Raluca Maltesen,Sture Falkmer
出处
期刊:Clinical Proteomics [BioMed Central]
卷期号:19 (1) 被引量:24
标识
DOI:10.1186/s12014-021-09339-5
摘要

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 (Log 2 FC = − 1.1, p = 0.0003, AUC = 0.82, 95% CI: 0.69–0.96) and complement factor H-related protein 4 (Log 2 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.
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