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

IF 3.2 4区医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Journal of Gene Medicine Pub Date : 2024-03-18 DOI:10.1002/jgm.3678

Jiajun Qin, Jin Fu, Xianzhen Chen

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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.

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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：对药物敏感性、分子亚型、免疫浸润和预后的见解。

研究目的本研究旨在研究组蛋白乙酰化对多形性胶质母细胞瘤（GBM）和低级别胶质瘤（LGG）的影响及其对患者预后的潜在影响。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之间的关系：本研究使用了提供全面基因组和临床信息的 TCGA-GBMLGG 数据集。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，计算出HAs。为评估组蛋白乙酰化相关基因的预后价值，还进行了 Kaplan-Meier 生存分析。此外，还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：我们的分析表明，HAs与患者的预后有明显的关联，HAs越高，GBM和LGG患者的预后越差。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，这表明它们在调节组蛋白乙酰化水平方面具有潜在作用。此外，我们还发现免疫检查点基因在高HAs组和低HAs组之间存在明显的表达差异，这表明组蛋白乙酰化对GBM和LGG患者的免疫反应有潜在影响：本研究强调了组蛋白乙酰化在GBM和LGG中的重要性。组蛋白乙酰化具有预后价值，表明其有可能成为临床相关的生物标记物。HAs与参与组蛋白乙酰化调控的关键基因之间的相关性，让人们深入了解了GBM和LGG中组蛋白乙酰化失调的潜在机制。此外，观察到的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存在潜在联系。这些发现有助于我们了解 GBM 和 LGG 的分子基础，并对针对组蛋白乙酰化和免疫微环境的个性化治疗方法具有重要意义。要证实这些发现并探索潜在的治疗策略，还需要进一步的验证和功能研究。

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来源期刊

Journal of Gene Medicine 医学-生物工程与应用微生物

CiteScore

6.40

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The aims and scope of The Journal of Gene Medicine include cutting-edge science of gene transfer and its applications in gene and cell therapy, genome editing with precision nucleases, epigenetic modifications of host genome by small molecules, siRNA, microRNA and other noncoding RNAs as therapeutic gene-modulating agents or targets, biomarkers for precision medicine, and gene-based prognostic/diagnostic studies. Key areas of interest are the design of novel synthetic and viral vectors, novel therapeutic nucleic acids such as mRNA, modified microRNAs and siRNAs, antagomirs, aptamers, antisense and exon-skipping agents, refined genome editing tools using nucleic acid /protein combinations, physically or biologically targeted delivery and gene modulation, ex vivo or in vivo pharmacological studies including animal models, and human clinical trials. Papers presenting research into the mechanisms underlying transfer and action of gene medicines, the application of the new technologies for stem cell modification or nucleic acid based vaccines, the identification of new genetic or epigenetic variations as biomarkers to direct precision medicine, and the preclinical/clinical development of gene/expression signatures indicative of diagnosis or predictive of prognosis are also encouraged.