To capture protease activity directly from plasma, we employed a panel of six CCP probes that were designed to both be cleaved by a diverse array of proteases and also target specific cancer-relevant proteases, including angiotensin-converting enzyme 2 (ACE2), cathepsin B (CATB), methionine aminopeptidases 1 and 2 (METAP1/2), matrix metalloproteinase 14 (MMP14), plasmin, and ubiquitin-specific peptidase 15 (USP15)16–22. Here, USP15 is linked to cancer.