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中性粒细胞胞外诱捕网相关风险评分可预测多发性骨髓瘤的预后并刻画肿瘤微环境

英文原题:A neutrophil extracellular trap-related risk score predicts prognosis and characterizes the tumor microenvironment in multiple myeloma.

查看英文原题

A neutrophil extracellular trap-related risk score predicts prognosis and characterizes the tumor microenvironment in multiple myeloma.

PubMed 2024/01/27(内容时间) Sci Rep Q1 · IF 4.9(JCR 2025)

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中文摘要

多发性骨髓瘤(MM)是一种显著的血液系统恶性肿瘤,现有研究已阐明其与中性粒细胞胞外诱捕网(NETs)的相互作用,后者可能潜在促进肿瘤生长。

然而,针对NETs在MM中作用的系统性研究仍然有限。利用单细胞数据集GSE223060,我们识别出活跃的NET细胞亚群,即中性粒细胞、单核细胞和巨噬细胞。随后构建了转录轨迹以理解MM的进展。此后,对MM中的细胞通讯进行了分析,特别关注中性粒细胞,揭示出相互作用增强但强度减弱,同时MM样本中中性粒细胞与NK细胞之间存在异常通讯链接。通过交叉分析NET活跃/非活跃细胞与MM对比健康样本之间的差异表达基因(DEGs),共鉴定出316个基因。这促成了基于总生存期的13基因风险模型用于预后预测,利用转录组数据集GSE136337。高风险组表现出免疫浸润改变和对化疗的敏感性增高。构建的预测生存概率的列线图在1年、3年和5年生存预测中显示出令人鼓舞的AUC值。

总体而言,我们的发现揭示了一种新的NET相关MM预后特征,从而为治疗探索提供了潜在途径。

展开英文摘要原文

Multiple myeloma (MM) is a distinguished hematologic malignancy, with existing studies elucidating its interaction with neutrophil extracellular traps (NETs), which may potentially facilitate tumor growth.

However, systematic investigations into the role of NETs in MM remain limited. Utilizing the single-cell dataset GSE223060, we discerned active NET cell subgroups, namely neutrophils, monocytes, and macrophages. A transcriptional trajectory was subsequently constructed to comprehend the progression of MM. Following this, an analysis of cellular communication in MM was conducted with a particular emphasis on neutrophils, revealing an augmentation in interactions albeit with diminished strength, alongside abnormal communication links between neutrophils and NK cells within MM samples.

Through the intersection of differentially expressed genes (DEGs) between NET active/inactive cells and MM versus healthy samples, a total of 316 genes were identified. This led to the development of a 13-gene risk model for prognostic prediction based on overall survival, utilizing transcriptomics dataset GSE136337.

The high-risk group manifested altered immune infiltration and heightened sensitivity to chemotherapy. A constructed nomogram for predicting survival probabilities demonstrated encouraging AUCs for 1, 3, and 5-year survival predictions. Collectively, our findings unveil a novel NET-related prognostic signature for MM, thereby providing a potential avenue for therapeutic exploration.

论文信息

作者
Zhao Z、Huo Y、Du Y、Huang Y、Liu H、Zhang C、Yan J
第一作者单位
Liaoning Key Laboratory of Hematopoietic Stem Cell Transplantation and Translational Medicine, Department of Hematology, Liaoning Medical Center for Hematopoietic Stem Cell Transplantation, The Second Hospital of Dalian Medical University, Dalian, 116023, China.China
通讯作者单位
Liaoning Key Laboratory of Hematopoietic Stem Cell Transplantation and Translational Medicine, Department of Hematology, Liaoning Medical Center for Hematopoietic Stem Cell Transplantation, The Second Hospital of Dalian Medical University, Dalian, 116023, China. yanjsdmu@dmu.edu.cn.China
期刊
Scientific reports2024 Jan 27
原文标识
PubMed 38278930 · DOI 10.1038/s41598-024-52922-7