Pedersen Shona, Jensen Katrine Papendick, Honoré Bent, Kristensen Søren Risom, Pedersen Camilla Holm, Szejniuk Weronika Maria, Maltesen Raluca Georgiana, Falkmer Ursula
Department of Basic Medical Sciences, College of Medicine, QU Health, Qatar University, 2713, Doha, Qatar.
Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
Clin Proteomics. 2022 Jan 7;19(1):2. doi: 10.1186/s12014-021-09339-5.
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.
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.
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 FC = - 1.1, p = 0.0003, AUC = 0.82, 95% CI: 0.69-0.96) and complement factor H-related protein 4 (Log 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.
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.
小细胞肺癌（SCLC）的早期检测迫切需要高度可靠的标志物。越来越多的证据表明，细胞外囊泡携带肿瘤细胞特异性物质，适合作为癌症中的蛋白质标志物。循环微泡和外泌体的定量蛋白质组分析可以成为发现新的分子见解和潜在标志物的高通量平台。因此，本研究旨在调查新诊断的SCLC患者血浆来源的微泡和外泌体的蛋白质组动态变化，以改善早期检测。
通过高速或超速离心从24名健康对照者和24名SCLC患者的血浆中分离出血浆来源的微泡和外泌体。使用无标记质谱法定量这些细胞外囊泡衍生的蛋白质，并进行统计分析，旨在识别SCLC患者和健康对照者之间显著改变的蛋白质表达。此外，对显著表达的蛋白质进行功能富集分析，以识别与SCLC发病机制相关的生物学途径。
基于变化倍数（FC）≥2或≤0.5以及曲线下面积（AUC）≥0.70（p<0.05），我们分别鉴定出微泡和外泌体的10种常见蛋白质以及16种和17种独特蛋白质。在这些蛋白质中，我们发现与健康个体相比，SCLC患者中凝血因子XIII A（Log FC = -1.1，p = 0.0003，AUC = 0.82，95%CI：0.69 - 0.96）和补体因子H相关蛋白4（Log FC = 1.2，p = 0.0005，AUC = 0.82，95%CI；0.67 - 0.97）失调。我们的数据可能表明凝血在SCLC发病机制中具有新的肿瘤抑制作用，并且补体激活参与其中。
在比较SCLC患者和健康个体时，鉴定出了几种差异表达的蛋白质。这是第一项表明循环细胞外囊泡可能包含具有SCLC潜在诊断特性的特定蛋白质的研究，从而为新型非侵入性标志物带来了新机遇。
