Exosome miRNAs profiling in serum and prognostic evaluation in patients with multiple myeloma.

IF 1.5 Q3 HEMATOLOGY
Teng Fang, Hao Sun, Xiyue Sun, Yi He, Peixia Tang, Lixin Gong, Zhen Yu, Lanting Liu, Shiyi Xie, Tingyu Wang, Zhenshu Xu, Shuhua Yi, Gang An, Yan Xu, Guoqing Zhu, Lugui Qiu, Mu Hao
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引用次数: 0

Abstract

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.

Abstract Image

Abstract Image

Abstract Image

多发性骨髓瘤患者血清外泌体mirna谱分析和预后评估。
外泌体携带的MicroRNAs (MiRNAs)在肿瘤微环境中细胞组分之间的串扰中起着关键作用。本研究旨在通过综合生物信息学分析,鉴定多发性骨髓瘤(MM)患者血清中外泌体miRNAs (exo-miRNAs)的表达谱,并研究其调控网络及其潜在功能。从19例新诊断MM患者和9例健康供者的血清中分离出外泌体,并通过小RNA测序研究其miRNA谱。计算外显子mirna的差异表达量,预测mirna的靶基因。应用CytoHubba鉴定中心mirna和核心靶基因。采用LASSO Cox回归模型建立预后模型,计算ESTIMATE免疫评分,探讨模型与MM患者免疫状态的相关性。鉴定出前6个中枢差异表达的血清外显mirna。在詹氏骨髓瘤微阵列数据集中,6个hub外显mirna的513个靶基因在MM细胞中被证实存在差异表达。功能富集分析表明,这些靶基因主要参与mRNA剪接、细胞应激反应和去泛素化。13个核心外显子mirna靶基因被应用于创建一个新的预后标记,为MM患者提供风险分层,这与MM患者的免疫微环境有关。我们的研究全面研究了MM患者的外显mirna谱。构建了一种新的预后特征,以促进具有不同结果的MM患者的风险分层。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
1.70
自引率
0.00%
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审稿时长
10 weeks
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