结直肠癌（CRC）是最常见的恶性疾病之一，通常在诊所中被晚期检测到。目前可用于CRC诊断的诊断工具要么侵入性较强，要么对早期病变不敏感，因为可靠生物标志物不足。在本研究中，我们发现CRC患者粪便中的细胞外囊泡（EVs）可以作为非侵入性诊断和预后的有效生物标志物。这一发现基于对粪便来源的EV（fEV）中的两种跨膜蛋白CD147和A33进行鉴定，这两种蛋白与CRC有内在关联。检测结果显示，CRC患者（n = 48）的fEV上CD147和A33的水平升高，与健康供体（n = 16）有明显区别。CD147/A33富集的EV在临床敏感性上提供了89％的临床敏感性，远高于临床已确认的血清生物标志物CEA（40％）。此外，对纵向粪便样本（n = 29）的分析表明，可以利用CD147/A33富集的fEV跟踪CRC的预后。由于基于粪便检测的高合规性，CD147/A33富集的fEV可以作为大规模非侵入性CRC筛选以及临床干预过程中患者结果的实时监测的新一代CRC生物标志物。©2023年作者。《细胞外囊泡杂志》由Wiley Periodicals，LLC代表国际细胞外囊泡学会出版。

Colorectal cancer (CRC) is one of the most common malignancies that is usually detected late in the clinic. The currently available diagnostic tools for CRC are either invasive or insensitive to early lesions due to the dearth of reliable biomarkers. In this study, we discovered that the extracellular vesicles (EVs) in the faeces of CRC patients can act as a potent biomarker for the non-invasive diagnosis and prognosis of CRC. This finding is based on the identification of two transmembrane proteins-CD147 and A33-on faeces-derived EVs (fEVs) that are intrinsically associated with CRC. The detection results show that the levels of CD147 and A33 on fEVs were upregulated in the CRC patients (n = 48), dramatically distinguishing them from the healthy donors (n = 16). The CD147/A33-enriched EVs offer a clinical sensitivity of 89%, much higher than that (40%) of carcinoembryonic antigen (CEA), a clinically-established serum biomarker for CRC diagnosis. In addition, the analysis of longitudinal faeces samples (n = 29) demonstrated that the CD147/A33-enriched fEVs can be utilized to track the prognosis of CRC. Due to the high compliance of faeces-based detection, the CD147/A33-enriched fEVs could serve as new-generation CRC biomarkers for large-scale, non-invasive CRC screening as well as real-time monitoring of patient outcomes during clinical interventions.© 2023 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.