Identification of faecal extracellular vesicles as novel biomarkers for the non‐invasive diagnosis and prognosis of colorectal cancer

Abstract

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. K E Y WO R D S biomarkers, clinical diagnosis, colorectal cancer, extracellular vesicles, faeces  INTRODUCTIONColorectal cancer (CRC) ranks third in common malignancies and is the second leading cause of death concerning cancer (Sung et al., 2021). Most CRCs develop from precursor lesions such as adenomatous polyps or sessile serrated lesions (Erichsen et al.,

Designing Multimodal Informative Sensing with an Exosome-Mediated Signal Coupling Transduction Strategy Based on a Single-Stimulus Multiresponse Recognition Interface

“…As observed, significant difference in ECL intensity, PA signal, and color value in the CRC patients group compared to healthy humans in Figure 5G. In addition, carcinoembryonic antigen (CEA) is a clinically established serum biomarker for CRC diagnosis, 47,48 but it needs to be combined with the clinical colonoscopy test, tissue analysis, and imaging to further diagnose CRC more accurately. Therefore, the above results were compared with those of comprehensive clinical diagnosis based on CEA-ELISA, and the results remained consistent (Table S3).…”

Extracellular vesicles in neuroblastoma: role in progression, resistance to therapy and diagnostics

“…Recent studies focusing on EV-miRNAs have indicated their significance as non-invasive biomarkers in different malignant tumors (62). Similarly, several studies have reported the presence of small RNAs and their potential application for NB prognosis.…”

“…EVs derived from adipocytes and adipose-endothelial cells were found to induce proliferation, migration and invasion of the recipient prostate cancer cells, thereby promoting metastasis in prostate cancer (64, 65). While CAFs were found to support the surrounding tumor cells by transferring tumor-supportive signals via EVs, thereby contributing to tumor growth and metastasis in several cancer types (62,(66)(67)(68). In addition, endothelial cell derived-EVs were shown to affect macrophages, by converting them to a M2-like phenotype thereby inducing an immunosuppressive environment and aiding in cancer progression (69).…”

Current Research on Molecular Biomarkers for Colorectal Cancer in Stool Samples

“…In this context, we found only one study that has looked for potential CRC biomarkers in fecal EVs (fEVs). Zhang et al, 2023 showed, by Western blot, immunogold transmission electron microscopy, immunofluorescence, and ELISA, that the levels of the proteins CD147 and cell surface A33 antigen on fEVs were higher in CRC patients, compared to healthy donors, with no significant variation across the different stages of CRC [95].…”