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整合多组学数据,从单细胞测序的角度识别自噬相关基因在肿瘤微环境中的作用以及胶质母细胞瘤的关键肿瘤发生因素。

Integrating multi-omics data to identify the role of Aggrephagy-related genes in tumor microenvironment and key tumorigenesis factors of GB from the perspective of single-cell sequencing.

作者信息

Chen Zipei, Zhang Shengke, Jiang Chenglu, Jiang Lai, Chen Haiqing, Huang Jinbang, Liu Jie, Yang Guanhu, Luo Xiufang, Chi Hao, Fu Jiangping

机构信息

Department of Oncology, Dazhou Central Hospital, Dazhou, 635000, China.

Department of Clinical, Clinical Medical College, Southwest Medical University, Luzhou, 646000, China.

出版信息

Discov Oncol. 2025 May 16;16(1):777. doi: 10.1007/s12672-025-02431-4.

DOI:10.1007/s12672-025-02431-4
PMID:40377747
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12084465/
Abstract

This study presents a pioneering exploration into the role of aggrephagy-related genes (ARGs) in glioblastoma (GB), a kind of malignant tumor which is highly invasive and resistant to a series of therapy. Utilizing single-cell sequencing to dissect their influence on the tumor microenvironment (TME) and tumorigenesis. By applying non-negative matrix factorization for dimensionality reduction and clustering of single-cell data, distinct cellular subtypes within the TME influenced by ARGs were identified, uncovering their functions and interactions. The investigation extends to validating the prognostic significance of ARGs and their potential in predicting immunotherapy outcomes. Molecular docking analysis of key ARGs further highlights TUBA1C and UBB as promising therapeutic targets, offering novel insights into GB's complex biology and suggesting a targeted approach for therapy, which is characterized by some crucial pathways in our analysis, including PI3k-akt and TGF-beta pathways. This comprehensive single-cell level examination not only advances our understanding of aggrephagy's role in GB but also proposes new avenues for prognosis and treatment strategies, emphasizing the critical impact of ARGs on the TME and GB progression.

摘要

本研究对自噬相关基因(ARGs)在胶质母细胞瘤(GB)中的作用进行了开创性探索,胶质母细胞瘤是一种具有高度侵袭性且对一系列治疗具有抗性的恶性肿瘤。利用单细胞测序来剖析其对肿瘤微环境(TME)和肿瘤发生的影响。通过应用非负矩阵分解对单细胞数据进行降维和聚类,确定了受ARGs影响的TME内不同的细胞亚型,揭示了它们的功能和相互作用。该研究还扩展到验证ARGs的预后意义及其在预测免疫治疗结果方面的潜力。对关键ARGs的分子对接分析进一步突出了TUBA1C和UBB作为有前景的治疗靶点,为GB复杂的生物学特性提供了新见解,并提出了一种靶向治疗方法,在我们的分析中其特征在于一些关键途径,包括PI3k-akt和TGF-β途径。这种全面的单细胞水平检查不仅推进了我们对自噬在GB中作用的理解,还为预后和治疗策略提出了新途径,强调了ARGs对TME和GB进展的关键影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3223/12084465/8aab65c51ed4/12672_2025_2431_Fig12_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3223/12084465/c23389bb3c42/12672_2025_2431_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3223/12084465/ac4f6b603f12/12672_2025_2431_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3223/12084465/6e979b2c58e3/12672_2025_2431_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3223/12084465/d932f7978d1b/12672_2025_2431_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3223/12084465/cd6fbd3bbe51/12672_2025_2431_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3223/12084465/147296b70b91/12672_2025_2431_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3223/12084465/a6477fbfb9ba/12672_2025_2431_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3223/12084465/7c008c8422a1/12672_2025_2431_Fig11_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3223/12084465/8aab65c51ed4/12672_2025_2431_Fig12_HTML.jpg

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