Li Xiaoou, Xiao Xiong, Wang Yi, Gu Guocan, Li Tian, Wang Yi, Li Chunzhao, Zhang Peng, Ji Nan, Zhang Yang, Zhang Liwei
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.
China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.
Cancers (Basel). 2024 Jan 3;16(1):228. doi: 10.3390/cancers16010228.
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.
本研究的目的是调查白细胞介素13受体α2（IL13Ra2）在脑干胶质瘤（BSG）中的表达及其与关键标志物、功能和预后的相关性，评估其治疗潜力。共分析了80例BSG患者的肿瘤样本。采用多重免疫荧光法检测六种标志物——IL13Ra2、H3.3K27M、CD133、Ki67、HLA-1和CD4——以确定IL13Ra2与这些标志物之间的关系。采用Kaplan-Meier和Cox比例风险回归模型进行生存分析，纳入了66例有完整随访资料的患者。使用DESeq2库分析了先前发表的一项涉及98例患者的研究中的RNA测序数据，以确定组间差异基因表达。通过clusterProfiler库进行基因本体（GO）富集和单样本基因集富集分析（ssGSEA），以描述差异表达基因（DEG）的基因功能。几乎所有BSG患者的IL13Ra2表达都有所不同，45.0%（36/80）的患者表达增加超过20%。在脑桥胶质瘤、弥漫性固有脑桥胶质瘤（DIPG）、H3F3A突变型胶质瘤和世界卫生组织（WHO）IV级胶质瘤中，显著观察到IL13Ra2水平升高。IL13Ra2表达与H3.3K27M突变蛋白、Ki67和CD133密切相关。与IL13Ra2表达≤20%的患者相比，表示>20%的患者总生存期较短。Cox比例风险回归模型确定H3F3A突变而非IL13Ra2表达为独立预后因素。对我们先前队列的RNA测序数据进行分析，证实了IL13Ra2与H3.3、CD133和Ki67水平的相关性。IL13Ra2在BSG中广泛表达，尤其是在H3F3A突变组中升高，与H3F3A突变、增殖增加和肿瘤干性增强密切相关。IL13Ra2是BSG的一个有前景的治疗靶点，可能使H3K27M突变、DIPG、WHO IV级和脑桥部位特异性BSG患者，尤其是H3K27M突变患者受益。
