Integrative single-cell and bulk transcriptome analyses identify a distinct pro-tumor macrophage signature that has a major prognostic impact on glioblastomas.

IF 3.2 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL
Peilin Li, Guolei Su, Yinglin Cui
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引用次数: 0

Abstract

Glioblastoma (GBM) is a highly heterogeneous disease with poor clinical outcomes. To comprehensively dissect the molecular landscape of GBM and heterogeneous macrophage clusters in the progression of GBM, this study integrates single-cell and bulk transcriptome data to recognize a distinct pro-tumor macrophage cluster significantly associated with the prognosis of GBM and develop a GBM prognostic signature to facilitate prior subtypes. Leveraging glioma single-cell sequencing data, we identified a novel pro-tumor macrophage subgroup, marked by S100A9, which might interact with endothelial cells to facilitate tumor progression via angiogenesis. To further benefit clinical application, a prognostic signature was established with the genes associated with pro-tumor macrophages. Patients classified within the high-risk group characterized with enrichment in functions related to tumor progression, including epithelial-mesenchymal transition and hypoxia, displays elevated mutations in the TERT promoter region, reduced methylation in the MGMT promoter region, poorer prognoses, and diminished responses to temozolomide therapy, thus effectively discriminating between the prognostic outcomes of GBM patients. Our research sheds light on the intricate microenvironment of gliomas and identifies potential molecular targets for the development of novel therapeutic approaches.

Abstract Image

单细胞和大体转录组的整合分析确定了对胶质母细胞瘤预后有重大影响的独特的促肿瘤巨噬细胞特征。
胶质母细胞瘤(GBM)是一种高度异质性疾病,临床疗效不佳。为了全面剖析GBM和异质性巨噬细胞集群在GBM进展过程中的分子图谱,本研究整合了单细胞和大容量转录组数据,识别出与GBM预后显著相关的独特的促肿瘤巨噬细胞集群,并建立了GBM预后特征,以便于预先分型。利用胶质瘤单细胞测序数据,我们发现了一个以S100A9为标志的新型促肿瘤巨噬细胞亚群,它可能与内皮细胞相互作用,通过血管生成促进肿瘤进展。为了进一步促进临床应用,我们利用与促肿瘤巨噬细胞相关的基因建立了预后特征。被归入高风险组的患者,其特征是富含与肿瘤进展相关的功能,包括上皮-间质转化和缺氧,TERT启动子区突变增加,MGMT启动子区甲基化减少,预后较差,对替莫唑胺治疗的反应减弱,从而有效区分了GBM患者的预后结果。我们的研究揭示了胶质瘤错综复杂的微环境,并确定了开发新型治疗方法的潜在分子靶点。
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
Clinical and Experimental Medicine
Clinical and Experimental Medicine 医学-医学:研究与实验
CiteScore
4.80
自引率
2.20%
发文量
159
审稿时长
2.5 months
期刊介绍: Clinical and Experimental Medicine (CEM) is a multidisciplinary journal that aims to be a forum of scientific excellence and information exchange in relation to the basic and clinical features of the following fields: hematology, onco-hematology, oncology, virology, immunology, and rheumatology. The journal publishes reviews and editorials, experimental and preclinical studies, translational research, prospectively designed clinical trials, and epidemiological studies. Papers containing new clinical or experimental data that are likely to contribute to changes in clinical practice or the way in which a disease is thought about will be given priority due to their immediate importance. Case reports will be accepted on an exceptional basis only, and their submission is discouraged. The major criteria for publication are clarity, scientific soundness, and advances in knowledge. In compliance with the overwhelmingly prevailing request by the international scientific community, and with respect for eco-compatibility issues, CEM is now published exclusively online.
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