Human plasma provides a minimally invasive source of circulating cancer biomarkers, yet its extreme protein dynamic range and interindividual heterogeneity hinder the detection of low-abundance, tumor-derived signals. In colorectal cancer (CRC), where early detection, risk stratification, and therapy monitoring remain major unmet needs, these analytical barriers limit clinical translation.
Here, we present a single-particle enrichment workflow that unites P2 nanoparticles with iST sample preparation and Spectronaut® 20 DIA analysis, enabling deeper proteome coverage, improved quantitative precision, and enhanced biological insights for human EDTA-plasma biomarker discovery.