细胞因子间的信息交流是肿瘤微环境中微小RNA（miRNA）通过胞外体（exosome）携带所起到的重要作用。我们的研究旨在鉴定多发性骨髓瘤（MM）患者血清中胞外体miRNA（exo-miRNA）的表达谱，并通过综合生物信息学分析来探讨其调控网络及潜在功能。我们分离了19例新诊断MM患者和9名健康供体血清中的胞外体，并通过小RNA测序技术对miRNA进行了分析。计算了exo-miRNA的差异表达，并预测了miRNA的靶基因。我们使用CytoHubba识别了核心miRNA和核心靶基因。使用LASSO Cox回归模型构建了预后模型，并计算了ESTIMATE免疫评分以研究模型与MM患者免疫状态的相关性。鉴定了六个顶级差异表达血清exo-miRNA。在Zhan Myeloma微阵列数据集中确认了这六个核心exo-miRNA的513个靶基因在MM细胞中的差异表达。功能富集分析表明这些靶基因主要参与了mRNA剪接、细胞对应应激和去泛素化过程。应用了13个核心exo-miRNA靶基因构建了一种新的预后标志，可为MM患者提供风险分层，与MM患者的免疫微环境相关。我们的研究全面地调查了MM患者的exo-miRNA表达谱。构建了一种新的预后标志，便于区分MM患者的不同预后结果。2023年中国医学协会（CMA）和中国医学科学院血液学研究所、北京协和医学院（IHCAMS）授权 Wolters Kluwer Health Inc.发表权威性中文医学论文作品。

MicroRNAs (MiRNAs) carried by exosomes play pivotal roles in the crosstalk between cell components in the tumor microenvironment. Our study aimed at identifying the expression profile of exosomal miRNAs (exo-miRNAs) in the serum of multiple myeloma (MM) patients and investigating the regulation networks and their potential functions by integrated bioinformatics analysis. Exosomes in serum from 19 newly diagnosed MM patients and 9 healthy donors were isolated and the miRNA profile was investigated by small RNA sequencing. Differential expression of exo-miRNAs was calculated and target genes of miRNAs were predicted. CytoHubba was applied to identify the hub miRNAs and core target genes. The LASSO Cox regression model was used to develop the prognostic model, and the ESTIMATE immune score was calculated to investigate the correlation between the model and immune status in MM patients. The top six hub differentially expressed serum exo-miRNAs were identified. 513 target genes of the six hub exo-miRNAs were confirmed to be differentially expressed in MM cells in the Zhan Myeloma microarray dataset. Functional enrichment analysis indicated that these target genes were mainly involved in mRNA splicing, cellular response to stress, and deubiquitination. 13 core exo-miRNA target genes were applied to create a novel prognostic signature to provide risk stratification for MM patients, which is associated with the immune microenvironment of MM patients. Our study comprehensively investigated the exo-miRNA profiles in MM patients. A novel prognostic signature was constructed to facilitate the risk stratification of MM patients with distinct outcomes.Copyright © 2023 The Authors. Published by Wolters Kluwer Health Inc., on behalf of the Chinese Medical Association (CMA) and Institute of Hematology, Chinese Academy of Medical Sciences & Peking Union Medical College (IHCAMS).