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胶质母细胞瘤和低级别胶质瘤中组蛋白乙酰化相关基因的综合分析:药物敏感性、分子亚型、免疫浸润和预后的见解。

Comprehensive analysis of histone acetylation-related genes in glioblastoma and lower-grade gliomas: Insights into drug sensitivity, molecular subtypes, immune infiltration, and prognosis.

机构信息

Department of Neurosurgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.

出版信息

J Gene Med. 2024 Mar;26(3):e3678. doi: 10.1002/jgm.3678.

Abstract

OBJECTIVES

The purpose of this research was to study the impact of histone acetylation on glioblastoma multiforme (GBM) and lower-grade gliomas (LGG) and its potential implications for patient prognosis. We aimed to assess the histone acetylation score (HAs) and its relationship with key genes involved in histone acetylation regulation.

METHOD

The TCGA-GBMLGG dataset, which provides comprehensive genomic and clinical information, was utilized for this study. We calculated the HAs by analyzing the expression levels of histone acetylation-related genes, including histone acetyltransferases and histone deacetylases, in GBM and LGG patients. Kaplan-Meier survival analysis was performed to evaluate the prognostic value of the HAs. Furthermore, correlation analysis and differential expression analysis were conducted to assess the relationship between the HAs and key genes involved in histone acetylation regulation, as well as the expression differences of immune checkpoint genes.

RESULTS

Our analysis revealed a significant association between the HAs and patient prognosis, with higher HAs correlating to poorer outcomes in GBM and LGG patients. We observed a positive correlation between the HAs and key genes involved in histone acetylation regulation, indicating their potential role in modulating histone acetylation levels. Moreover, we found significant expression differences for immune checkpoint genes between high and low HAs groups, suggesting a potential impact of histone acetylation on the immune response in GBM and LGG.

CONCLUSION

This study highlights the significance of histone acetylation in GBM and LGG. The HAs demonstrated prognostic value, indicating its potential as a clinically relevant biomarker. The correlation between the HAs and key genes involved in histone acetylation regulation provides insights into the underlying mechanisms driving histone acetylation dysregulation in GBM and LGG. Furthermore, the observed expression differences of immune checkpoint genes suggest a potential link between histone acetylation and the immune response. These findings contribute to our understanding of the molecular basis of GBM and LGG and have implications for personalized treatment approaches targeting histone acetylation and the immune microenvironment. Further validation and functional studies are needed to confirm these findings and explore potential therapeutic strategies.

摘要

目的

本研究旨在探讨组蛋白乙酰化对胶质母细胞瘤(GBM)和低级别胶质瘤(LGG)的影响及其对患者预后的潜在意义。我们旨在评估组蛋白乙酰化评分(HAs)及其与参与组蛋白乙酰化调控的关键基因的关系。

方法

本研究使用 TCGA-GBMLGG 数据集,该数据集提供了全面的基因组和临床信息。我们通过分析组蛋白乙酰化相关基因(包括组蛋白乙酰转移酶和组蛋白去乙酰化酶)在 GBM 和 LGG 患者中的表达水平来计算 HAs。采用 Kaplan-Meier 生存分析评估 HAs 的预后价值。此外,我们进行了相关性分析和差异表达分析,以评估 HAs 与参与组蛋白乙酰化调控的关键基因之间的关系,以及免疫检查点基因的表达差异。

结果

我们的分析表明,HAs 与患者预后之间存在显著关联,较高的 HAs 与 GBM 和 LGG 患者的不良预后相关。我们观察到 HAs 与参与组蛋白乙酰化调控的关键基因之间存在正相关,表明它们在调节组蛋白乙酰化水平方面可能发挥作用。此外,我们发现高 HAs 和低 HAs 组之间免疫检查点基因的表达存在显著差异,提示组蛋白乙酰化可能对 GBM 和 LGG 的免疫反应产生影响。

结论

本研究强调了组蛋白乙酰化在 GBM 和 LGG 中的重要性。HAs 具有预后价值,表明其作为一种具有临床相关性的生物标志物的潜力。HAs 与参与组蛋白乙酰化调控的关键基因之间的相关性提供了组蛋白乙酰化失调在 GBM 和 LGG 中驱动机制的见解。此外,观察到免疫检查点基因的表达差异表明组蛋白乙酰化与免疫反应之间可能存在联系。这些发现有助于我们理解 GBM 和 LGG 的分子基础,并为针对组蛋白乙酰化和免疫微环境的个体化治疗方法提供了启示。需要进一步的验证和功能研究来证实这些发现并探索潜在的治疗策略。

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