Tokumura Kazuya, Hinoi Eiichi
Department of Bioactive Molecules, Pharmacology, Gifu Pharmaceutical University.
United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University.
Biol Pharm Bull. 2025;48(9):1319-1324. doi: 10.1248/bpb.b25-00219.
Glioblastoma (GBM) is a highly aggressive and lethal brain tumor with very poor prognosis despite recent progress in multimodal treatments. Within glioma tissue, various niche cells such as macrophages and neutrophils form a unique glioma immune microenvironment (GIME) by interacting with heterogenous cancer cells, and this has been implicated in disease progression and responsiveness to immunomodulatory therapies. This study explores novel potential prognostic markers associated with the GIME using integrated bioinformatics analyses, including single-cell RNA-sequencing (scRNA-seq), and spatial transcriptome (ST) datasets of clinical GBM specimens. We first identified 42 genes as being associated with poor prognosis in GBM from 5 different cohorts, GBM vs. nontumor tissue, grade IV vs. grade II gliomas, isocitrate dehydrogenase (IDH)-wild-type vs. IDH-mutant variants, mesenchymal vs. proneural and classical subtypes, and hazard ratio for overall survival. Among these, 32 genes were positively correlated with ESTIMATEScore, infiltration of various immune cell types, expression of known immune-related genes, and representative immune-associated biological signals. On scRNA-seq analysis, 7 genes were relatively concentrated in tumor-associated macrophages rather than in malignant cells. ST analysis revealed that Collagen beta(1-O)galactosyltransferase 1 (COLGALT1), Integrin subunit beta 2 (ITGB2), and Myosin light chain 12A (MYL12A) were distributed in the interface between the tumor and the peritumoral area, overlapping with the expression of representative immune-related genes. These findings support the potential of COLGALT1, ITGB2 and MYL12A as biomarkers for predicting the prognosis and immune responses of GBM, which can help in the development of potential immunotherapeutic strategies for GBM.
胶质母细胞瘤（GBM）是一种极具侵袭性和致命性的脑肿瘤，尽管多模式治疗取得了进展，但其预后仍然很差。在胶质瘤组织中，各种生态位细胞，如巨噬细胞和中性粒细胞，通过与异质性癌细胞相互作用，形成了独特的胶质瘤免疫微环境（GIME），这与疾病进展和免疫调节治疗的反应性有关。本研究使用综合生物信息学分析，包括单细胞RNA测序（scRNA-seq）和临床GBM标本的空间转录组（ST）数据集，探索与GIME相关的新型潜在预后标志物。我们首先从5个不同队列中确定了42个与GBM预后不良相关的基因，这些队列包括GBM与非肿瘤组织、IV级与II级胶质瘤、异柠檬酸脱氢酶（IDH）野生型与IDH突变型变体、间充质与前体神经及经典亚型，以及总生存风险比。其中，32个基因与ESTIMATEScore、各种免疫细胞类型的浸润、已知免疫相关基因的表达以及代表性免疫相关生物信号呈正相关。在scRNA-seq分析中，7个基因相对集中在肿瘤相关巨噬细胞而非恶性细胞中。ST分析显示，胶原蛋白β(1-O)半乳糖基转移酶1（COLGALT1）、整合素亚基β2（ITGB2）和肌球蛋白轻链12A（MYL12A）分布在肿瘤与瘤周区域的界面，与代表性免疫相关基因的表达重叠。这些发现支持COLGALT1、ITGB2和MYL12A作为预测GBM预后和免疫反应的生物标志物的潜力，这有助于开发GBM的潜在免疫治疗策略。
