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

Sonia M Setayesh; Libere J Ndacayisaba; Kate E Rappard; Valerie Hennes; Luz Yurany Moreno Rueda; Guilin Tang; Pei Lin; Robert Z Orlowski; David E Symer; Elisabet E Manasanch; Stephanie N Shishido; Peter Kuhn

doi:10.1038/s41698-023-00446-0

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

NPJ Precis Oncol. 2023 Sep 18;7(1):95. doi: 10.1038/s41698-023-00446-0.

Authors

Affiliations

¹ Convergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA, 90089, USA.
² Department of Lymphoma and Myeloma, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
³ Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
⁴ Convergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA, 90089, USA. sshishid@usc.edu.
⁵ Convergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA, 90089, USA. pkuhn@usc.edu.
⁶ Catherine & Joseph Aresty Department of Urology, Institute of Urology, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA. pkuhn@usc.edu.
⁷ Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA. pkuhn@usc.edu.
⁸ Department of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA, 90089, USA. pkuhn@usc.edu.
⁹ Department of Aerospace and Mechanical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA, 90089, USA. pkuhn@usc.edu.
¹⁰ Department of Biological Sciences, Dornsife College of Letters, Arts, and Sciences, University of Southern California, Los Angeles, CA, 90089, USA. pkuhn@usc.edu.

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.

Abstract

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