The objective of this study was to investigate IL13Ra2 expression in brainstem glioma (BSG) and its correlation with key markers, functions, and prognostic implications, evaluating its therapeutic potential. A total of 80 tumor samples from BSG patients were analyzed. Multiplex immunofluorescence was used to examine six markers—IL13Ra2, H3.3K27M, CD133, Ki67, HLA-1, and CD4—establishing relationships between IL13Ra2 and these markers. Survival analysis, employing Kaplan–Meier and Cox proportional hazard regression models, encompassed 66 patients with complete follow-up. RNA-Seq data from a previously published study involving 98 patients were analyzed using the DESeq2 library to determine differential gene expression between groups. Gene Ontology (GO) enrichment and single-sample gene set enrichment analysis (ssGSEA) via the clusterProfiler library were used to delineate the gene functions of differentially expressed genes (DEGs). Nearly all the BSG patients displayed varying IL13Ra2 expression, with 45.0% (36/80) exhibiting over a 20% increase. Elevated IL13Ra2 levels were notably observed in pontine gliomas, diffuse intrinsic pontine gliomas (DIPGs), H3F3A-mutant gliomas, and WHO IV gliomas. IL13Ra2 expression was strongly correlated with H3.3K27M mutant protein, Ki67, and CD133. Patients with IL13Ra2 expression >20% showed shorter overall survival compared to those with ≤20% IL13Ra2 expression. The Cox proportional hazard regression model identified H3F3A mutations, rather than IL13Ra2 expression, as an independent prognostic factor. Analysis of RNA-Seq data from our prior cohort confirmed IL13Ra2’s correlation with H3.3, CD133, and Ki67 levels. Widespread IL13Ra2 expression in BSG, particularly elevated in the H3F3A mutant group, was strongly correlated with H3F3A mutations, increased proliferation, and heightened tumor stemness. IL13Ra2 represents a promising therapeutic target for BSGs, potentially benefiting patients with H3K27M mutations, DIPGs, WHO Grade IV, and pontine location-specific BSGs, particularly those with H3K27M mutations.
本研究旨在探讨脑干胶质瘤（BSG）中IL13Ra2的表达情况，及其与关键标志物、功能和预后影响的关联，以评估其治疗潜力。研究共分析了80例BSG患者的肿瘤样本。采用多重免疫荧光技术检测了六种标志物——IL13Ra2、H3.3K27M、CD133、Ki67、HLA-1和CD4，并建立了IL13Ra2与这些标志物之间的关系。生存分析采用Kaplan-Meier法和Cox比例风险回归模型，涵盖了66例具有完整随访资料的患者。利用DESeq2软件包分析了先前一项涉及98例患者的已发表研究中的RNA-Seq数据，以确定组间差异基因表达。通过clusterProfiler软件包进行基因本体（GO）富集分析和单样本基因集富集分析（ssGSEA），以阐明差异表达基因（DEGs）的基因功能。几乎所有BSG患者均表现出不同程度的IL13Ra2表达，其中45.0%（36/80）的患者IL13Ra2表达增加超过20%。在脑桥胶质瘤、弥漫内生型脑桥胶质瘤（DIPG）、H3F3A突变型胶质瘤和WHO IV级胶质瘤中，IL13Ra2水平显著升高。IL13Ra2表达与H3.3K27M突变蛋白、Ki67和CD133呈强相关。与IL13Ra2表达≤20%的患者相比，IL13Ra2表达>20%的患者总生存期更短。Cox比例风险回归模型确定H3F3A突变（而非IL13Ra2表达）为独立的预后因素。对我们先前队列的RNA-Seq数据分析证实，IL13Ra2与H3.3、CD133和Ki67水平相关。IL13Ra2在BSG中广泛表达，尤其在H3F3A突变组中表达升高，且与H3F3A突变、增殖增加和肿瘤干细胞性增强密切相关。IL13Ra2是BSG一个有前景的治疗靶点，可能使H3K27M突变、DIPG、WHO IV级以及脑桥特定部位BSG患者受益，尤其是那些伴有H3K27M突变的患者。
Expression of Interleukin-13 Receptor Alpha 2 in Brainstem Gliomas
肿瘤(癌症)患者之家