通过对小细胞外囊泡的蛋白质组学分析发现结肠癌的诊断生物标志物。

BACKGROUND: Small extracellular vesicles (small-EVs) are membranous vesicles that contain unique information regarding the condition of cells and contribute to the recruitment and reprogramming of components associated with the tumor environment. Therefore, many researchers have suggested that small-EV proteins are potential biomarkers for diseases such as cancer. Colon cancer (CC) is one of the most common causes of cancer-related deaths worldwide. Biomarkers such as carcinoembryonic antigen (CEA) show low sensitivity (~ 40%), and thus the demand for novel biomarkers for CC diagnosis is increasing. METHODS: In this study, we identified biomarkers for diagnosing CC through proteomic analysis of small-EVs from CC cell lines. These small-EVs were characterized by western blot analysis, nanoparticle tracking analysis, and transmission electron microscopy and analyzed using mass spectrometry. RESULTS: Five selected proteins were found to be upregulated in CC by western blot analysis. Among the candidate proteins, tetraspanin 1 (TSPAN1) was found to be upregulated in plasma EVs from CC patients compared to those from healthy controls (HCs) with 75.7% sensitivity. CONCLUSIONS: These results suggest that TSPAN1 is a potent non-invasive biomarker for CC detection. Our experimental strategy provides useful insights into the identification of cancer-specific non-invasive biomarkers.

背景：小细胞外囊泡（small-EVs）是含有关于细胞状况的独特信息的膜性囊泡，有助于募集和重编程与肿瘤环境相关的成分。因此，许多研究人员认为 small-EV 蛋白是癌症等疾病的潜在生物标志物。结肠癌（CC）是全球癌症相关死亡的最常见原因之一。癌胚抗原（CEA）等生物标志物的灵敏度较低（约 40%），因此对 CC 诊断的新型生物标志物的需求不断增加。

方法：在本研究中，我们通过对 CC 细胞系的 small-EVs 进行蛋白质组学分析，鉴定用于诊断 CC 的生物标志物。通过 Western blot 分析、纳米颗粒跟踪分析和透射电子显微镜对这些 small-EVs 进行了表征，并使用质谱进行了分析。

结果：Western blot 分析发现 5 种选定的蛋白质在 CC 中上调。在候选蛋白中，与健康对照（HC）相比，TSPAN1 在 CC 患者的血浆 EVs 中上调，灵敏度为 75.7%。

结论：这些结果表明 TSPAN1 是 CC 检测的一种有效的非侵入性生物标志物。我们的实验策略为鉴定癌症特异性的非侵入性生物标志物提供了有用的见解。