Jeong Hyesun, Choi Byeong Hyeon, Park JinA, Jung Jik-Han, Shin Hyunku, Kang Ka-Won, Quan Yu Hua, Yu Jewon, Park Ji-Ho, Park Yong, Choi Yeonho, Kim Hyun Koo, Hong Sunghoi
School of Biosystems and Biomedical Sciences, Korea University, Seoul 02841, Korea.
BK21 FOUR R&E Center for Precision Public Health, Graduate School of Korea University, Seoul 02855, Korea.
Cancers (Basel). 2021 Oct 31;13(21):5482. doi: 10.3390/cancers13215482.
No specific markers have been identified to detect non-small cell lung cancer (NSCLC) cell-derived exosomes circulating in the blood. Here, we report a new biomarker that distinguishes between cancer and non-cancer cell-derived exosomes. Exosomes isolated from patient plasmas at various pathological stages of NSCLC, NSCLC cell lines, and human pulmonary alveolar epithelial cells isolated using size exclusion chromatography were characterized. The GRIP and coiled-coil domain-containing 2 (GCC2) protein, involved in endosome-to-Golgi transport, was identified by proteomics analysis of NSCLC cell line-derived exosomes. GCC2 protein levels in the exosomes derived from early-stage NSCLC patients were higher than those from healthy controls. Receiver operating characteristic curve analysis revealed the diagnostic sensitivity and specificity of exosomal GCC2 to be 90% and 75%, respectively. A high area under the curve, 0.844, confirmed that GCC2 levels could effectively distinguish between the exosomes. These results demonstrate GCC2 as a promising early diagnostic biomarker for NSCLC.
尚未鉴定出用于检测血液中循环的非小细胞肺癌(NSCLC)细胞衍生外泌体的特异性标志物。在此,我们报告一种区分癌症和非癌细胞衍生外泌体的新型生物标志物。对通过尺寸排阻色谱法从NSCLC不同病理阶段患者血浆、NSCLC细胞系以及人肺泡上皮细胞中分离出的外泌体进行了表征。通过对NSCLC细胞系衍生外泌体的蛋白质组学分析,鉴定出参与内体到高尔基体运输的含GRIP和卷曲螺旋结构域2(GCC2)蛋白。早期NSCLC患者衍生外泌体中的GCC2蛋白水平高于健康对照。受试者工作特征曲线分析显示,外泌体GCC2的诊断敏感性和特异性分别为90%和75%。曲线下面积为0.844,证实GCC2水平可有效区分外泌体。这些结果表明GCC2是一种有前景的NSCLC早期诊断生物标志物。