← 返回

H3K27 突变型儿童弥漫性中线胶质瘤中的免疫抑制微环境:关于 CD8A、IL7R 和 ICAM1 的单细胞与生物信息学见解

英文原题:Immunosuppressive Microenvironment in H3K27 Mutant Pediatric Diffuse Midline Glioma: Single-Cell and Bioinformatics Insights on CD8A, IL7R, and ICAM1.

查看英文原题

Immunosuppressive Microenvironment in H3K27 Mutant Pediatric Diffuse Midline Glioma: Single-Cell and Bioinformatics Insights on CD8A, IL7R, and ICAM1.

PubMed 2025/01/01(内容时间) Curr Med Chem Q2 · IF 3.2(JCR 2025)

分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。

研究概要

我们研究的综合发现表明,CD8A、IL7R 和 ICAM1 可能作为诊断和预后评估儿童 DMG 的新型生物标志物。此外,这些分子有望成为治疗该疾病的靶点。我们研究的意义强调了探索这些新途径以改善患者预后的重要性。

研究思路结论见上方概要

弥漫性中线胶质瘤(DMG)作为一种主要影响儿童脑桥区域的恶性肿瘤,构成了严重威胁。这类肿瘤对治疗干预表现出明显且高度的耐药性,并具有极强的侵袭性行为。

在本研究中,我们从基因表达综合数据库(GEO)获取了DMG数据。随后,我们进行了功能注释,并开展了通路富集分析以及基因集富集分析(GSEA)。通过构建蛋白质-蛋白质相互作用(PPI)网络,我们识别出了关键的枢纽基因。为了评估这些枢纽基因对免疫浸润的影响,我们采用了CIBERSORT算法。此外,为了支持我们的发现,我们进行了单细胞分析。

我们的研究结果表明,CD8A、IL7R和ICAM1参与了针对多种免疫细胞类型的免疫反应,如T细胞、中性粒细胞、NK细胞、树突状细胞、γδ T细胞和M1型巨噬细胞。此外,包括IDO1和TIGIT在内的免疫检查点的存在可能促进了肿瘤内免疫抑制,从而促进了儿童DMG侵袭性表型的发展和耐药性的产生。

展开英文摘要原文

Diffuse midline gliomas (DMG) pose a grave threat as a malignant tumor primarily affecting children in the pons region. These tumors exhibit a distinct and heightened resistance to therapeutic interventions, coupled with exceptionally aggressive behavior.

In this study, we accessed DMG data from the Gene Expression Omnibus (GEO) database. Subsequently, we performed functional annotation and conducted pathway enrichment analysis as well as gene set enrichment analysis (GSEA). Constructing a protein-protein interaction (PPI) network, we identified pivotal hub genes. To evaluate the impact of these hub genes on immune infiltration, we employed the CIBERSORT algorithm. Furthermore, to bolster our findings, we conducted a single-cell analysis.

Our findings indicate the involvement of CD8A, IL7R, and ICAM1 in immune responses targeting diverse immune cell types, such as T cells, neutrophils, NK cells, dendritic cells, γδ T cells, and Macrophages M1. Additionally, the presence of immune checkpoints, including IDO1 and TIGIT, likely contributes to intratumoral immunosuppression, thereby fostering the development of an aggressive phenotype and resistance in pediatric DMG.

In conclusion, the collective findings of our study suggest the potential role of CD8A, IL7R, and ICAM1 as innovative biomarkers for diagnosing and prognosticating pediatric DMG. Moreover, these molecules hold promise as therapeutic targets in the management of this disease. The implications of our research underscore the importance of exploring these novel avenues for improved patient outcomes.

论文信息

作者
Huang J、You G、Chen Q、Lin Y、Lin Y、Liang Y、Lin C、Chen J
第一作者单位
Department of Neurosurgery, Affiliated Hospital of Putian University, Putian, 351100, China.China
通讯作者单位
Department of Radiation Oncology, Fujian Medical University Union Hospital, Fuzhou, Fujian province, China.China
期刊
Current medicinal chemistry2025
原文标识
PubMed 38347782 · DOI 10.2174/0109298673280120240108045926