Targeted single-cell proteomic analysis identifies new liquid biopsy biomarkers associated with multiple myeloma

Abstract Multiple myeloma (MM) is accompanied by alterations to the normal plasma cell (PC) proteome, leading to changes to the tumor microenvironment and disease progression. There is a great need for understanding the consequences that lead to MM progression and for the discovery of new biomarkers that can aid clinical diagnostics and serve as targets for therapeutics. This study demonstrates the applicability of utilizing the single-cell high-definition liquid biopsy assay (HDSCA) and imaging mass cytometry to characterize the proteomic profile of myeloma. In our study, we analyzed ~87,000 cells from seven patient samples (bone marrow and peripheral blood) across the myeloma disease spectrum and utilized our multiplexed panel to characterize the expression of clinical markers for PC classification, additional potential therapeutic targets, and the tumor microenvironment cells. Our analysis showed BCMA, ICAM3 (CD50), CD221, and CS1 (SLAMF7) as the most abundantly expressed markers on PCs across all myeloma stages, with BCMA, ICAM3, and CD221 having significantly higher expression levels on disease versus precursor PCs. Additionally, we identify significantly elevated levels of expression for CD74, MUM1, CD229, CD44, IGLL5, Cyclin D1, UBA52, and CD317 on PCs from overt disease conditions compared to those from precursor states