Paradeisi Foteini, Tserga Aggeliki, Lygirou Vasiliki, Makridakis Manousos, Stroggilos Rafael, Georgiou Grigoris, Spyrou George M, Kostopoulos Ioannis V, Liacos Christine-Ivy, Termentzi Aikaterini, Dimopoulos Meletios A, Tsitsilonis Ourania, Vlahou Antonia, Kastritis Efstathios, Zoidakis Jerome
Department of Biotechnology, Biomedical Research Foundation, Academy of Athens, Athens, Greece.
Bioinformatics Department, The Cyprus Institute of Neurology & Genetics, Nicosia, Cyprus.
Proteomics. 2025 Aug;25(16):48-60. doi: 10.1002/pmic.70025. Epub 2025 Aug 7.
Multiple myeloma (MM) remains incurable; gaps in our understanding of MM molecular pathogenesis and drugs' resistance mechanisms are involved in the failure of therapies. This study aims to identify proteins significantly impacting MM patients' response to commonly used therapeutic regimens. Bone marrow CD138+ selected plasma cells were isolated from patients who had achieved Response (Responders, R) and those who were Non-Responders (NR) to their primary MM therapy. We used LC-MS/MS to investigate the proteomic profile of MM samples, followed by bioinformatics analysis. We identified 1190 proteins, of which 230 showed a statistically significant difference between R and NR, with 27 proteins being upregulated and 203 downregulated in R compared to NR. Pathway enrichment analysis identified pathways related to the immune response and protein synthesis regulation, closely associated with MM progression and response to therapy. The results were validated through individual RNA dataset analysis, corroborating the differential expression of several proteins, including proteins associated with MM (e.g., MIF, ILF3) as well as novel findings (e.g., DCPS and SET). Collectively, proteomics data obtained from R and NR to MM therapy displayed significant changes in the immune system and protein synthesis regulation, supporting their potential role in progression and therapeutic response of MM.
多发性骨髓瘤（MM）仍然无法治愈；我们对MM分子发病机制和药物耐药机制的理解存在差距，这与治疗失败有关。本研究旨在鉴定对MM患者对常用治疗方案的反应有显著影响的蛋白质。从对其原发性MM治疗有反应（反应者，R）和无反应（无反应者，NR）的患者中分离出骨髓CD138 +选择的浆细胞。我们使用液相色谱-串联质谱法（LC-MS/MS）研究MM样本的蛋白质组学概况，随后进行生物信息学分析。我们鉴定出1190种蛋白质，其中230种在R和NR之间显示出统计学上的显著差异，与NR相比，R中有27种蛋白质上调，203种下调。通路富集分析确定了与免疫反应和蛋白质合成调节相关的通路，这些通路与MM进展和对治疗的反应密切相关。通过个体RNA数据集分析验证了结果，证实了几种蛋白质的差异表达，包括与MM相关的蛋白质（例如，MIF、ILF3）以及新发现（例如，DCPS和SET）。总体而言，从MM治疗的R和NR中获得的蛋白质组学数据显示免疫系统和蛋白质合成调节有显著变化，支持它们在MM进展和治疗反应中的潜在作用。
