The inter-tumor heterogeneity of the tumor microenvironment (TME) and how it correlates with clinical profiles and biological characteristics in brainstem gliomas (BSGs) remain unknown, dampening the development of novel therapeutics against BSGs. The TME status was determined with a list of pan-cancer conserved gene expression signatures using a single-sample gene set enrichment analysis (ssGSEA) and was subsequently clustered via consensus clustering. BSGs exhibited a high inter-tumor TME heterogeneity and were classified into four clusters: “immune-enriched, fibrotic”, “immune-enriched, non-fibrotic”, “fibrotic”, and “depleted”. The “fibrotic” cluster had a higher proportion of diffuse intrinsic pontine gliomas (p= 0.041), and “PA-like” tumors were more likely to be “immune-enriched, fibrotic” (p= 0.044). The four TME clusters exhibited distinct overall survival (p< 0.001) and independently impacted BSG outcomes. A four-gene panel as well as a radiomics approach were constructed to identify the TME clusters and achieved high accuracy for determining the classification. Together, BSGs exhibited high inter-tumor heterogeneity in the TME and were classified into four clusters with distinct clinical outcomes and tumor biological properties. The TME classification was accurately identified using a four-gene panel that can potentially be examined with the immunohistochemical method and a non-invasive radiomics method, facilitating its clinical application.
脑干胶质瘤（BSGs）的肿瘤微环境（TME）存在显著的瘤间异质性，且其与临床特征及生物学特性的关联尚不明确，这阻碍了针对BSGs的新型治疗方法的开发。本研究通过单样本基因集富集分析（ssGSEA）利用一组泛癌保守基因表达特征确定了TME状态，并采用共识聚类法进行聚类分析。结果显示，BSGs表现出高度的瘤间TME异质性，可划分为四个亚群：“免疫富集-纤维化型”、“免疫富集-非纤维化型”、“纤维化型”和“贫乏型”。其中，“纤维化型”亚群中弥漫内生型脑桥胶质瘤的比例较高（p=0.041），而“毛细胞星形细胞瘤样”肿瘤更倾向于属于“免疫富集-纤维化型”（p=0.044）。这四种TME亚群在总生存期上表现出显著差异（p<0.001），且独立影响BSGs的预后。研究构建了一个四基因组合及影像组学方法用于识别TME亚群，并在分类判定中实现了高准确性。综上所述，BSGs在TME中具有高度瘤间异质性，可分为四个具有不同临床预后和肿瘤生物学特性的亚群。通过可经免疫组化方法验证的四基因组合及无创的影像组学方法，能够准确识别TME分类，为其临床应用提供了便利。
Classification of Brainstem Gliomas Based on Tumor Microenvironment Status
肿瘤(癌症)患者之家