Serum protein fingerprinting by PEA immunoassay coupled with a pattern-recognition algorithms distinguishes MGUS and multiple myeloma

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// Petra Schneiderova 1, * , Tomas Pika 2, * , Petr Gajdos 3 , Regina Fillerova 1 , Pavel Kromer 3 , Milos Kudelka 3 , Jiri Minarik 2 , Tomas Papajik 2 , Vlastimil Scudla 2 and Eva Kriegova 1 1 Department of Immunology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic 2 Department of Hemato-Oncology, Faculty of Medicine and Dentistry, Palacky University and University Hospital, Olomouc, Czech Republic 3 Department of Computer Science, Faculty of Electrical Engineering and Computer Science, VSB-Technical University of Ostrava, Ostrava, Czech Republic * These authors have contributed equally to this work Correspondence to: Eva Kriegova, email: eva.kriegova@email.cz Keywords: serum pattern, cytokines, growth factors, proximity extension immunoassay, post-transplant serum pattern Received: May 04, 2016 Accepted: July 28, 2016 Published: August 12, 2016 ABSTRACT Serum protein fingerprints associated with MGUS and MM and their changes in MM after autologous stem cell transplantation (MM-ASCT, day 100) remain unexplored. Using highly-sensitive Proximity Extension ImmunoAssay on 92 cancer biomarkers (Proseek Multiplex, Olink), enhanced serum levels of Adrenomedullin (ADM, P corr = .0004), Growth differentiation factor 15 (GDF15, P corr = .003), and soluble Major histocompatibility complex class I-related chain A (sMICA, P corr = .023), all prosurvival and chemoprotective factors for myeloma cells, were detected in MM comparing to MGUS. Comparison of MGUS and healthy subjects revealed elevation of angiogenic and antia-poptotic midkine ( P corr = .0007) and downregulation of Transforming growth factor beta 1 (TGFB1, P corr = .005) in MGUS. Importantly, altered serum pattern was associated with MM-ASCT compared to paired MM at the diagnosis as well as to healthy controls, namely by upregulated B-Cell Activating Factor (sBAFF) ( P corr < .006) and sustained elevation of other pro-tumorigenic factors. In conclusion, the serum fingerprints of MM and MM-ASCT were characteristic by elevated levels of prosurvival and chemoprotective factors for myeloma cells.

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