Serum proteome profiling identified thrombospondin-1 and lactoferrin as biomarkers of relapsed multiple myeloma

Introduction Multiple myeloma (MM) remains an incurable hematologic malignancy characterized by inevitable relapse despite advances in novel therapeutics. Identifying reliable biomarkers for relapsed/refractory MM (RRMM) is crucial to improving clinical outcomes. Methods We conducted a comprehensive proteomic analysis of bone marrow and peripheral serum samples from newly diagnosed MM (NDMM), RRMM, and MM remission patients, along with healthy controls. Using tandem mass tag (TMT)-labeled quantitative mass spectrometry, we quantified over 1,000 serum proteins. Identified candidate proteins were further validated via ELISA. Results Thrombospondin-1 (THBS1) and lactoferrin (LTF) were significantly downregulated in the bone marrow serum of RRMM patients. ELISA validation confirmed markedly reduced levels of THBS1 and LTF in both bone marrow and peripheral serum of RRMM patients compared to NDMM, remission, and healthy control groups. Discussion Our integrated proteomic and biochemical analyses suggest that the THBS1/LTF protein signature may serve as a predictive biomarker for MM relapse. This signature offers potential clinical utility in disease monitoring and therapeutic stratification.