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分子谱揭示了不同亚型髓母细胞瘤的免疫相关标志物。

Molecular profile reveals immune-associated markers of medulloblastoma for different subtypes.

机构信息

Department of Neuro-oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

School of Mechatronical Engineering, Beijing Institute of Technology, Beijing, China.

出版信息

Front Immunol. 2022 Jul 28;13:911260. doi: 10.3389/fimmu.2022.911260. eCollection 2022.

Abstract

Medulloblastoma, a common pediatric malignant tumor, has been recognized to have four molecular subgroups [wingless (WNT), sonic hedgehog (SHH), group 3, group 4], which are defined by the characteristic gene transcriptomic and DNA methylomic profiles, and has distinct clinical features within each subgroup. The tumor immune microenvironment is integral in tumor initiation and progression and might be associated with therapeutic responses. However, to date, the immune infiltrative landscape of medulloblastoma has not yet been elucidated. Thus, we proposed MethylCIBERSORT to estimate the degree of immune cell infiltration and weighted correlation network analysis (WGCNA) to find modules of highly correlated genes. Synthesizing the hub genes in the protein-protein interaction (PPI) network and modules of the co-expression network, we identify three candidate biomarkers [GRB2-associated-binding protein 1 (GAB1), Abelson 1 (ABL1), and CXC motif chemokine receptor type 4 (CXCR4)] the molecular profiles of medulloblastoma. Given this, we investigated the correlation between these three immune hub genes and immune checkpoint blockade response and the potential of drug prediction further. In addition, this study demonstrated a higher presence of endothelial cells and infiltrating immune cells in Group 3 tumor bulk. The above results will be conducive to better comprehending the immune-related pathogenesis and treatment of medulloblastoma.

摘要

髓母细胞瘤是一种常见的儿童恶性肿瘤,现已被确认具有四个分子亚群[无翅型(WNT)、声波刺猬(SHH)、第 3 组、第 4 组],这些亚群是通过特征性的基因转录组和 DNA 甲基化组谱来定义的,并且在每个亚群中都具有不同的临床特征。肿瘤免疫微环境在肿瘤的发生和发展中起着重要作用,并且可能与治疗反应有关。然而,迄今为止,髓母细胞瘤的免疫浸润景观尚未阐明。因此,我们提出了 MethylCIBERSORT 来估计免疫细胞浸润的程度,并用加权相关网络分析(WGCNA)来寻找高度相关基因的模块。综合蛋白质-蛋白质相互作用(PPI)网络中的枢纽基因和共表达网络的模块,我们确定了三个候选生物标志物[GRB2 相关结合蛋白 1(GAB1)、ABL1 和 CXC 基序趋化因子受体 4(CXCR4)],用于髓母细胞瘤的分子图谱。鉴于此,我们进一步研究了这三个免疫枢纽基因与免疫检查点阻断反应的相关性及其药物预测的潜力。此外,本研究表明,在第 3 组肿瘤中存在更多的内皮细胞和浸润免疫细胞。上述结果将有助于更好地理解髓母细胞瘤的免疫相关发病机制和治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a615/9367478/23510a0e4abf/fimmu-13-911260-g001.jpg

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