基于单细胞分析结合生物信息学的胶质瘤关键生物标志物和免疫微环境特征鉴定。

IF 2.9 4区 医学 Q3 ENDOCRINOLOGY & METABOLISM
Yang Zhang, Lisha Liu, Chao Peng, Lu Wang, Jun Yang, Yingjiang Gu, Yu Cai
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引用次数: 0

摘要

胶质瘤是中枢神经系统(CNS)的高度侵袭性和异质性肿瘤,其特点是预后差,治疗困难。对其分子机制的全面理解仍然是当前研究的关键焦点和挑战。本研究旨在结合生物信息学和单细胞分析技术,探索胶质瘤相关细胞类型和免疫细胞浸润特征,为胶质瘤的分子发病机制提供新的认识,寻找潜在的治疗靶点。从Gene expression Omnibus (GEO)中选择基因表达谱,并从GeneCards中获得胶质瘤相关基因数据集。单细胞分析用于鉴定细胞类型,生物信息学技术用于鉴定胶质瘤的潜在致病靶点。构建蛋白-蛋白相互作用(PPI)网络,利用基因本体(GO)和京都基因与基因组百科全书(KEGG)数据库进行功能富集分析。最终通过药物靶点预测和分子对接分析揭示了潜在药物的作用机制。单细胞分析鉴定出10种细胞类型,其中小胶质细胞和少突胶质细胞在胶质瘤中起关键作用。分子生物学分析鉴定出20个关键基因。GO和KEGG分析表明,这些中心基因主要富集在细胞组分组织或生物发生、细胞过程、细胞连接和催化活性等过程中。主要涉及的信号通路包括p53信号通路、细胞周期和细胞衰老。此外,分子对接结果显示槲皮素有效结合4个枢纽靶点(DLGAP5、TOP2A、CHEK1、MKI67),提示槲皮素可能通过作用于这些靶点来改善胶质瘤相关的生物学特性。综上所述,本研究不仅揭示了特定细胞类型和关键基因在胶质瘤中的重要作用,而且初步阐明了槲皮素作为潜在治疗剂的分子机制,为未来胶质瘤干预策略提供了坚实的理论基础和新的研究方向。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Identification of key biomarkers and immune microenvironment features in gliomas based on single-cell analysis combined with bioinformatics.

Gliomas are highly invasive and heterogeneous tumors in the central nervous system (CNS), characterized by poor prognosis and significant therapeutic challenges. The comprehensive understanding of their molecular mechanisms remains a critical focus and challenge in current research. This study aims to integrate bioinformatics and single-cell analysis technologies to explore glioma-related cell types and immune cell infiltration features, providing new insights into the molecular pathogenesis of gliomas and identifying potential therapeutic targets. Gene expression profiles were selected from Gene Expression Omnibus (GEO), and a glioma-related gene dataset was obtained from GeneCards. Single-cell analysis was employed to identify cell types, and bioinformatics techniques were applied to identify potential pathogenic targets in gliomas. A protein-protein interaction (PPI) network was constructed, followed by functional enrichment analysis using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Ultimately, drug target prediction and molecular docking analysis revealed the mechanisms of potential drugs. Single-cell analysis identified 10 cell types, with microglial cells and oligodendrocytes playing crucial roles in gliomas. Molecular biological analysis identified 20 key genes. GO and KEGG analyses indicated that these hub genes were primarily enriched in processes such as cellular component organization or biogenesis, cellular processes, cell junctions, and catalytic activity. The main signaling pathways involved include the p53 signaling pathway, cell cycle, and cellular senescence. Furthermore, molecular docking results showed that quercetin effectively binds to four hub targets (DLGAP5, TOP2A, CHEK1, MKI67), suggesting that quercetin may improve glioma-related biological features by acting on these targets. In conclusion, this study not only reveals the significant roles of specific cell types and key genes in gliomas but also preliminarily elucidates the molecular mechanisms of quercetin as a potential therapeutic agent, providing a solid theoretical foundation and new research directions for future glioma intervention strategies.

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来源期刊
Discover. Oncology
Discover. Oncology Medicine-Endocrinology, Diabetes and Metabolism
CiteScore
2.40
自引率
9.10%
发文量
122
审稿时长
5 weeks
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