Background:Cancer-associated fibroblasts (CAFs) are key components of the glioblastoma (GBM) microenvironment and contribute to tumor progression, immune evasion, and therapy resistance. However, their heterogeneity and clinical impact in GBM remain poorly defined.Methods:We performed an integrative transcriptomic analysis combining bulk and single-cell RNA sequencing (scRNA-seq) datasets to characterize CAF subtypes in GBM. Four CAF-associated transcriptional programs were defined based on canonical gene signatures: immune CAFs, myofibroblastic CAFs (myoCAFs), inflammatory CAFs (iCAFs), and antigen-presenting CAFs (apCAFs). Prognostic relevance was assessed using survival analyses, and hub genes were identified through network analysis.Results:CAF subtype-specific gene signatures were significantly associated with poor overall survival. Single-cell analysis revealed spatial heterogeneity of CAF activation, with immune and inflammatory CAF markers enriched in low-stemness tumor cells. SYK was identified as a central hub gene shared across CAF subtypes, suggesting its role in stromal signaling.Conclusions:Our study reveals CAF subtype-associated patterns with prognostic and functional relevance in GBM. Targeting CAF subpopulations and key mediators such as SYK may represent a promising therapeutic strategy in GBM.
背景：癌症相关成纤维细胞（CAF）是胶质母细胞瘤（GBM）微环境的关键组成部分，参与肿瘤进展、免疫逃逸和治疗抵抗。然而，其在GBM中的异质性及临床影响尚不明确。 方法：我们整合了批量与单细胞RNA测序数据集进行转录组学综合分析，以表征GBM中的CAF亚型。基于经典基因特征定义了四种CAF相关转录程序：免疫型CAF、肌成纤维型CAF、炎症型CAF和抗原呈递型CAF。通过生存分析评估其预后相关性，并利用网络分析鉴定枢纽基因。 结果：CAF亚型特异性基因特征与患者不良总生存期显著相关。单细胞分析揭示了CAF活化的空间异质性，其中免疫与炎症型CAF标志物在低干性肿瘤细胞中富集。SYK被鉴定为跨CAF亚型共享的核心枢纽基因，提示其在基质信号传导中的重要作用。 结论：本研究揭示了GBM中具有预后与功能相关性的CAF亚型特征模式。靶向CAF亚群及SYK等关键介质可能成为GBM潜在的治疗策略。
肿瘤(癌症)患者之家