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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.
摘要：
胶质母细胞瘤（GBM）是一种高度异质性的疾病，临床预后较差。为了全面剖析GBM的分子景观和GBM进展中的异质巨噬细胞簇，这项研究整合了单细胞和批量转录组数据,以识别与GBM预后显著相关的独特的前肿瘤巨噬细胞簇,并开发GBM预后标志以促进以前的亚型.利用神经胶质瘤单细胞测序数据，我们确定了一个新的促肿瘤巨噬细胞亚群，以S100A9为标志，可能与内皮细胞相互作用，通过血管生成促进肿瘤进展。进一步有利于临床应用,利用与肿瘤前巨噬细胞相关的基因建立了预后特征.属于高危人群的患者，其特征是与肿瘤进展相关的功能富集，包括上皮-间质转化和缺氧，在TERT启动子区域显示升高的突变，MGMT启动子区域的甲基化减少，较差的预后，对替莫唑胺治疗的反应减弱，从而有效区分GBM患者的预后结果。我们的研究揭示了神经胶质瘤复杂的微环境，并确定了开发新治疗方法的潜在分子靶标。
