Wu Xiaoxiao, Guo Jianying, Deng Haiteng, Chen Wenming
Department of Comprehensive Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing, China.
Front Med (Lausanne). 2025 Sep 8;12:1640245. doi: 10.3389/fmed.2025.1640245. eCollection 2025.
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.
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.
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.
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.
多发性骨髓瘤（MM）仍然是一种无法治愈的血液系统恶性肿瘤，尽管新型治疗方法取得了进展，但仍不可避免地会复发。识别复发/难治性多发性骨髓瘤（RRMM）的可靠生物标志物对于改善临床结果至关重要。
我们对新诊断的MM（NDMM）、RRMM和MM缓解患者以及健康对照的骨髓和外周血血清样本进行了全面的蛋白质组分析。使用串联质谱标签（TMT）标记的定量质谱法，我们对1000多种血清蛋白进行了定量。通过ELISA进一步验证鉴定出的候选蛋白。
血小板反应蛋白-1（THBS1）和乳铁蛋白（LTF）在RRMM患者的骨髓血清中显著下调。ELISA验证证实，与NDMM、缓解和健康对照组相比，RRMM患者骨髓和外周血血清中THBS1和LTF水平明显降低。
我们的综合蛋白质组学和生化分析表明，THBS1/LTF蛋白特征可能作为MM复发的预测生物标志物。这种特征在疾病监测和治疗分层方面具有潜在的临床应用价值。
