Yan Xiuyou, Feng Lu, Xu Zhengbao, Chen Wei, Yan Hao, Wu Panxing, Ding Chao, Zhu Xuanhao, Lu Yansong
The Department of Neurosurgery, Taizhou Central Hospital, Taizhou, Zhejiang, China.
The Department of Neurosurgery, Xinchang County People's Hospital, Shaoxing, Zhejiang, China.
J Gene Med. 2023 Oct;25(10):e3511. doi: 10.1002/jgm.3511. Epub 2023 Apr 25.
Glioblastoma (GBM) is a primary malignant tumour with high intracranial morbidity, high malignancy and poor prognosis. Abnormal changes in histone acetylation are closely related to the occurrence and development of cancer. However, there is still a lack of systematic research on histone acetylation in GBM.
Whole-transcriptome sequencing data and clinical data of GBM patients were obtained through the TCGA database. Single-cell RNA-sequencing (scRNA-seq) data from GBM patients were obtained from GSE146711 in the Gene Expression Omnibus database. Cell descending fractionation was first performed for scRNA-seq on GBM. The CellChat and PROGENy scores explore the impact of the histone acetylation pathway in GBM on intercellular chat and tumour pathways. The AddModuleScore function evaluates the enrichment score of histone acetylation in cells and divides them into high-histone acetylation and low-histone acetylation groups. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed on the differential genes between different histone acetylation states, and the biological processes and pathways that may be affected by histone acetylation were evaluated. Based on this, a prognostic model was constructed using least absolute shrinkage and selection operator (LASSO) analysis, and survival analysis was performed to evaluate its prognostic performance. Finally, we also analysed the main effects of the constructed histone acetylation-related model on GBM immune infiltration by multiple methods, and analysed the main mutation data of its different subgroups.
GBM samples mainly include seven large cell populations: oligodendrocyte precursor cells (OPCs), myeloid, neoplastic, oligodendrocytes, astrocytes, vascular and neurons. Cellchat and ProgenY scores revealed that in GBM tumours, histone acetylation interacts closely with multiple immune cells and tumour pathways. GO and KEGG analyses revealed the main impact proteins and pathway correlates of histone acetylation. Five histone acetylation genes were screened using LASSO analysis and a prognostic model was constructed. The results revealed that prognostic models were significant in the prognostic stratification of patients in both the training and validation groups of GBM patients. Immune infiltration analysis revealed that the mechanism of histone acetylation in GBM may be related to the immune infiltration of multiple effector immune cells.
Our histone acetylation-based biomarkers are closely associated with immune microenvironmental infiltration and functional mutations in multiple tumour pathways in GBM. This suggests that histone acetylation may reveal microscopic alterations in the tumour microenvironment, and may provide potential evidence and a research basis for the development of novel therapeutic targets for GBM. On this basis, a novel perspective on the spatial biology and immunological understanding of GBM is provided.
胶质母细胞瘤（GBM）是一种原发性恶性肿瘤，具有高颅内发病率、高恶性程度和不良预后。组蛋白乙酰化的异常变化与癌症的发生和发展密切相关。然而，关于GBM中组蛋白乙酰化仍缺乏系统研究。
通过TCGA数据库获取GBM患者的全转录组测序数据和临床数据。从基因表达综合数据库中的GSE146711获取GBM患者的单细胞RNA测序（scRNA-seq）数据。首先对GBM进行scRNA-seq的细胞降维分群。CellChat和PROGENy评分探讨GBM中组蛋白乙酰化途径对细胞间通讯和肿瘤途径的影响。AddModuleScore函数评估细胞中组蛋白乙酰化的富集评分，并将其分为高组蛋白乙酰化组和低组蛋白乙酰化组。对不同组蛋白乙酰化状态之间的差异基因进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析，评估可能受组蛋白乙酰化影响的生物学过程和途径。基于此，使用最小绝对收缩和选择算子（LASSO）分析构建预后模型，并进行生存分析以评估其预后性能。最后，我们还通过多种方法分析了构建的组蛋白乙酰化相关模型对GBM免疫浸润的主要影响，并分析了其不同亚组的主要突变数据。
GBM样本主要包括七个大的细胞群体：少突胶质前体细胞（OPC）、髓系细胞、肿瘤细胞、少突胶质细胞、星形胶质细胞、血管细胞和神经元。Cellchat和ProgenY评分显示，在GBM肿瘤中，组蛋白乙酰化与多种免疫细胞和肿瘤途径密切相互作用。GO和KEGG分析揭示了组蛋白乙酰化的主要影响蛋白和途径相关性。使用LASSO分析筛选出五个组蛋白乙酰化基因并构建了预后模型。结果显示，预后模型在GBM患者的训练组和验证组患者的预后分层中均具有显著性。免疫浸润分析表明，GBM中组蛋白乙酰化的机制可能与多种效应免疫细胞的免疫浸润有关。
我们基于组蛋白乙酰化的生物标志物与GBM中多个肿瘤途径的免疫微环境浸润和功能突变密切相关。这表明组蛋白乙酰化可能揭示肿瘤微环境中的微观改变，并可能为GBM新治疗靶点的开发提供潜在证据和研究基础。在此基础上，提供了关于GBM空间生物学和免疫学理解的新视角。
