关键补体调节因子在胶质母细胞瘤中的过表达
Overexpression of key complement regulators in glioblastoma.
摘要(中文译文)
胶质母细胞瘤（GBM）是成人中最常见且恶性程度最高的原发性脑肿瘤。尽管免疫逃逸是GBM进展公认的驱动因素，也是有效免疫治疗的主要障碍，但补体系统的作用仍未被充分探索。C1抑制剂（C1-INH）作为一种补体激活调节因子，近期被发现于GBM中过表达。因此，我们假设GBM除C1-INH外还过表达其他补体调节因子，本研究旨在鉴定这些因子。我们在九个公开可用的转录组数据集中分析了补体抑制剂、补体调节因子五聚蛋白-3（PTX3）以及补体蛋白的基因表达。在每个数据集中，对每个基因在样本组间进行了统计学比较。差异表达的补体抑制剂通过免疫染色在大鼠GBM细胞系NS1和患者来源的GBM组织中进行蛋白质水平的验证。编码因子I的CFI在GBM中较非肿瘤脑组织显著过表达，而编码血栓调节蛋白和因子H的THBD和CFH则呈现中度过表达。编码C1-INH的SERPING1同样上调，证实了此前的发现。免疫染色证实了这些抑制剂在体外以及人胶质母细胞瘤组织中的表达。此外，PTX3和早期补体蛋白在GBM中显著过表达，而C5及下游成分的水平与正常脑组织相当。我们的研究结果表明，GBM肿瘤过表达一组特定的补体调节因子及补体级联成分，可能抑制了有效的抗肿瘤免疫应答。因此，将这些调节因子作为GBM潜在治疗靶点进行进一步研究具有高度必要性。
Abstract
Glioblastoma (GBM) is the most prevalent and malignant primary brain tumor in adults. While immune evasion is a well-recognized driver of GBM progression and a major obstacle for efficient immunotherapy, the role of the complement system remains underexplored. C1-inhibitor (C1-INH), a regulator of complement activation, was recently found overexpressed in GBM. We therefore hypothesized that GBM overexpresses additional complement regulators beyond C1-INH and the present work aimed to identify these. Gene expression of complement inhibitors, the complement regulator pentraxin-3 (PTX3), and complement proteins was analyzed across nine publicly available transcriptomic datasets. Within each dataset, statistical comparisons were performed between sample groups for each gene. Differentially expressed complement inhibitors were validated at the protein level by immunostaining in the rat GBM cell line NS1 and patient derived GBM tissue. CFI, encoding factor I, was significantly overexpressed in GBM compared to non-tumoral brain, while THBD and CFH, encoding thrombomodulin and factor H, displayed moderate overexpression. SERPING1, encoding C1-INH, was also upregulated, confirming previous findings. Immunostaining confirmed the expression of these inhibitors in vitro as well as in human glioblastoma tissue. Additionally, PTX3 and early complement proteins were significantly overexpressed in GBM, while levels of C5 and downstream components were comparable to normal brain. Our findings indicate that the GBM tumor overexpresses a specific set of complement regulators and components of the complement cascade, possibly inhibiting an efficient anti-tumoral immune response. Further investigations of these regulators as potential therapeutical targets in GBM are therefore highly warranted.
如何引用
AMA
Linnea Blomberg, Leonora Raba, Johan Bengzon, Kurt Osther, Henrietta Nittby Redebrandt. Overexpression of key complement regulators in glioblastoma.. PloS one. 2026; doi:10.1371/journal.pone.0349101.
APA
Linnea Blomberg, Leonora Raba, Johan Bengzon, Kurt Osther, Henrietta Nittby Redebrandt (2026). Overexpression of key complement regulators in glioblastoma.. PloS one. https://doi.org/10.1371/journal.pone.0349101
GB/T 7714
Linnea Blomberg, Leonora Raba, Johan Bengzon, Kurt Osther, Henrietta Nittby Redebrandt. Overexpression of key complement regulators in glioblastoma.[J]. PloS one, 2026 doi:10.1371/journal.pone.0349101.
在 PubMed增强版 阅读全文
翻译全文 · AI 文献问答 · PDF 原文下载 · 引用导出