Small extracellular vesicles (sEVs) are emerging as critical mediators of intercellular communication and as promising biomarkers for cancer detection. Our study compares the glycomic and proteomic profiles of sEVs from healthy individuals (H1-H5) and breast cancer patients (C0-C4) compared to their respective total plasma and sEV-depleted plasma fractions.
Our N-glycan analysis shows high-mannose, hybrid and bisecting glycans exhibit selective enrichment in sEVs compared to their respective total plasma, highlighting stage-specific glycan alterations in sEVs during cancer progression whereas the sEVs-depleted plasma shows a profile rich in tri and tetra-antennary complex sialylated and fucosylated glycans. These sEV related glycan modifications are frequently linked with tumor progression1, immune evasion and altered cell signalling2.
Proteomic profiling also identified the enrichment of several tumor associated glycosylated proteins in sEVs, such as Galectin-1, Integrin alpha-V, Laminin alpha-5, Heat Shock Protein 70, and Coagulation Factor XIII, many of which play crucial roles in extracellular matrix remodeling, metastasis, and immune suppression—key pathways in cancer progression3.
These findings highlight the selective molecular enrichment in sEVs compared to total plasma, reinforcing the potential of sEVs as a more specific biomarker source for cancer diagnostics. Both the specific glycomic and glycoproteomic enrichment in sEVs raises the question of how sEVs function in tumor progression. Future studies integrating advanced glycomic and proteomic approaches will be essential to unravel the structural modifications of these biomolecules and their functional implications in breast cancer.
1. De Leoz ML, et.al., Molecular & Cellular Proteomics. 2011 Jan 1;10(1).
2. Rodrigues JG, et.al., Cellular immunology. 2018 Nov 1;333:46-57.
3. Lucotti S, et.al., The EMBO journal. 2022 Sep 15;41(18):e109288.