Department of Laboratory Medicine, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, China.
Department of Laboratory Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
BMC Cancer. 2023 Jul 3;23(1):614. doi: 10.1186/s12885-023-10886-3.
Small extracellular vesicles (sEVs) have great potential as new biomarkers in liquid biopsy. However, due to the limitations of sEVs extraction and component analysis procedures, further clinical applications of sEVs are hampered. Carcinoembryonic antigen (CEA) is a commonly used broad-spectrum tumor marker that is strongly expressed in a variety of malignancies.
In this study, CEA sEVs were directly separated from serum using immunomagnetic beads, and the nucleic acid to protein ultraviolet absorption ratio (NPr) of CEA sEVs was determined. It was found that the NPr of CEA sEVs in tumor group was higher than that of healthy group. We further analyzed the sEV-derived nucleic acid components using fluorescent staining and found that the concentration ratio of double-stranded DNA to protein (dsDPr) in CEA sEVs was also significantly different between the two groups, with a sensitivity of 100% and a specificity of 41.67% for the diagnosis of pan-cancer. The AUC of dsDPr combined with NPr was 0.87 and the ACU of dsDPr combined with CA242 could reach 0.94, showing good diagnostic performance for pan-cancer.
This study demonstrates that the dsDPr of CEA sEVs can effectively distinguish sEVs derived from tumor patients and healthy individuals, which can be employed as a simple and cost-effective non-invasive screening technology to assist tumor diagnosis.
小细胞外囊泡（sEVs）作为液体活检中的新型生物标志物具有巨大潜力。然而，由于 sEVs 提取和成分分析程序的限制，sEVs 的进一步临床应用受到阻碍。癌胚抗原（CEA）是一种常用的广谱肿瘤标志物，在多种恶性肿瘤中强烈表达。
在本研究中，使用免疫磁珠直接从血清中分离 CEA sEVs，并测定 CEA sEVs 的核酸与蛋白质紫外吸光度比值（NPr）。结果发现，肿瘤组 CEA sEVs 的 NPr 高于健康组。我们进一步分析了 sEV 衍生的核酸成分，发现 CEA sEVs 中的双链 DNA 与蛋白质的浓度比（dsDPr）在两组之间也有显著差异，对泛癌的诊断具有 100%的灵敏度和 41.67%的特异性。dsDPr 联合 NPr 的 AUC 为 0.87，dsDPr 联合 CA242 的 ACU 可达 0.94，对泛癌具有良好的诊断性能。
本研究表明，CEA sEVs 的 dsDPr 能够有效区分来源于肿瘤患者和健康个体的 sEVs，可作为一种简单、经济有效的非侵入性筛选技术辅助肿瘤诊断。
