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胶质母细胞瘤干细胞:MAP17作为一种与静止和免疫逃逸相关的新型预测性生物标志物及治疗靶点

Glioblastoma Stem Cells: MAP17 as a Novel Predictive Biomarker and Therapeutic Target Associated with Quiescence and Immune Evasion.

作者信息

Aghamiri Sara Sadat, Amin Rada

机构信息

Department of Biochemistry, University of Nebraska, Lincoln, NE 68503, USA.

出版信息

Discov Med. 2025 Jan;37(192):166-181. doi: 10.24976/Discov.Med.202537192.14.

Abstract

BACKGROUND

Glioblastoma multiforme (GBM) is one of the deadliest and most heterogeneous forms of brain cancer, characterized by its resistance to conventional therapies. Within GBM, a subpopulation of slow-cycling cells, often linked to quiescence and stemness, plays a crucial role in treatment resistance and tumor recurrence. This study aimed to identify novel biomarkers associated with these slow-cycling GBM cells.

METHODS

We utilized The Cancer Genome Atlas (TCGA)-GBM dataset and presented the reproducible bioinformatics analysis for our results.

RESULTS

Our analysis highlighted Membrane-Associated Protein 17 () as strongly associated with the slow-cycling phenotype. We found that the protein cargo expression is related to mesenchymal signatures and stem cell-related pathways. Also, was linked to a distinct metabolic profile, characterized by significant enrichment in pathways related to folate, zinc, and fatty acids. Moreover, the immune cell distribution analysis revealed that correlates with key molecular immune processes, including interferon-gamma () signaling and antigen presentation, as well as immunosuppressive cells like myeloid-derived suppressor cells (MDSCs) and macrophages. -high tumors also showed elevated expression of several immune checkpoint inhibitors, indicating an immunosuppressive microenvironment.

CONCLUSION

These findings provide insight into the role of in quiescence, stemness, and immune evasion, positioning it as a promising therapeutic target.

摘要

背景

多形性胶质母细胞瘤(GBM)是最致命且异质性最强的脑癌形式之一,其特征是对传统疗法具有抗性。在GBM中,一个慢周期细胞亚群,通常与静止状态和干性相关,在治疗抗性和肿瘤复发中起关键作用。本研究旨在鉴定与这些慢周期GBM细胞相关的新型生物标志物。

方法

我们利用癌症基因组图谱(TCGA)-GBM数据集,并对我们的结果进行了可重复的生物信息学分析。

结果

我们的分析突出了膜相关蛋白17()与慢周期表型密切相关。我们发现蛋白货物表达与间充质特征和干细胞相关途径有关。此外,与独特的代谢谱相关,其特征是在与叶酸、锌和脂肪酸相关的途径中显著富集。此外,免疫细胞分布分析显示与关键的分子免疫过程相关,包括干扰素-γ()信号传导和抗原呈递,以及免疫抑制细胞如骨髓来源的抑制细胞(MDSCs)和巨噬细胞。高肿瘤还显示出几种免疫检查点抑制剂的表达升高,表明存在免疫抑制微环境。

结论

这些发现为在静止、干性和免疫逃逸中的作用提供了见解,将其定位为一个有前景的治疗靶点。

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