School of Medicine and Life Sciences, University of Jinan, Shandong Academy of Medical Sciences, Jinan, China.
Department of Clinical Laboratory, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, China.
Cancer Sci. 2019 Jan;110(1):433-442. doi: 10.1111/cas.13862. Epub 2018 Dec 6.
Accumulating evidence supports a role for exosomal protein in diagnosis. The purpose of this study was to identify the tumor-derived exosomal biomarkers in the serum that improve the diagnostic value in Chinese non-small cell lung cancer (NSCLC) patients. Serum exosomes were isolated from healthy donors (n = 46) and NSCLC patients (n = 125) by ultracentrifugation and were characterized using transmission electron microscopy, qNano, and immunoblotting. Proteomic profiles (by mass spectrometry) revealed multiple differentially expressed proteins in the healthy and NSCLC groups. The exosomal expression levels of alpha-2-HS-glycoprotein (AHSG) and extracellular matrix protein 1 (ECM1) increased significantly in the NSCLC patients compared to the healthy group. Alpha-2-HS-glycoprotein showed diagnostic values with a maximum area under the receiver operating characteristic curve (AUC) as 0.736 for NSCLC vs healthy individuals (P < .0001) and 0.682 for early stage NSCLC vs healthy individuals (P < .01). Extracellular matrix protein 1 showed the diagnostic capacity with AUC values of 0.683 (P < .001) and 0.656 (P < .05) in cancer and early stage NSCLC compared to healthy individuals. When AHSG was combined with ECM1, the AUCs were 0.795 and 0.739 in NSCLC and early stage patients, respectively. Taken together, the combination of AHSG, ECM1, and carcinoembryonic antigen improved the diagnostic potential of NSCLC. The diagnosis values were AUC of 0.938 for NSCLC and 0.911 for early stage NSCLC vs healthy individuals. Our results suggest that novel proteomic signatures found in serum exosomes of NSCLC patients show potential usefulness as diagnostic tools.
越来越多的证据支持外泌体蛋白在诊断中的作用。本研究旨在鉴定血清中肿瘤来源的外泌体生物标志物，以提高中国非小细胞肺癌（NSCLC）患者的诊断价值。通过超速离心从健康供体（n=46）和 NSCLC 患者（n=125）中分离血清外泌体，并通过透射电子显微镜、qNano 和免疫印迹进行表征。蛋白质组学图谱（质谱法）显示健康组和 NSCLC 组之间存在多种差异表达的蛋白质。与健康组相比，NSCLC 患者的外泌体中α-2-HS-糖蛋白（AHSG）和细胞外基质蛋白 1（ECM1）的表达水平显著升高。α-2-HS-糖蛋白对 NSCLC 与健康个体的诊断价值最大，曲线下面积（AUC）为 0.736（P<.0001），对早期 NSCLC 与健康个体的诊断价值为 0.682（P<.01）。细胞外基质蛋白 1 在癌症和早期 NSCLC 与健康个体相比，AUC 值分别为 0.683（P<.001）和 0.656（P<.05），具有诊断能力。当 AHSG 与 ECM1 联合使用时，NSCLC 和早期阶段患者的 AUC 值分别为 0.795 和 0.739。综上所述，联合 AHSG、ECM1 和癌胚抗原可提高 NSCLC 的诊断潜能。AUC 值分别为 0.938（NSCLC 与健康个体）和 0.911（早期 NSCLC 与健康个体）。我们的研究结果表明，在 NSCLC 患者血清外泌体中发现的新蛋白质组学特征具有作为诊断工具的潜在用途。
