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Multi-omics approaches establishing histone modification based prognostic model in glioma patients and further verification of the carcinogenesis mechanism

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Abstract

Glioblastoma (GBM) emerges as the most common malignant brain tumor. Histone modifications, as an epigenetic regulatory mechanism of gene expression, are closely associated with malignant tumors. Gene set related to histone modification was extracted from the MSigDB database, and scored by the function of AddModuleScore. Pearson correlation analysis was utilized using the “rcorr” function of “Hmisc” R package. Genes were screened out using the LASSO Cox analysis. TCGA-GBM and CGGA_array_301 cohorts were employed for constructing model and validation. We calculated immune infiltration scores using microenvironment cell populations counter (MCPcounter), single-sample gene set enrichment analysis (ssGSEA), and xCell algorithms. U87-MG and CHG-5 cell lines were utilized to evaluate expression level of TMEM176A by western blot (WB). Transwell, EDU, colony formation analysis (CFA), and CKK-8 assays were conducted to investigate cell proliferation and migration rate. The malignant cells in GBM patients exhibited notable activation in the TGF-β and hypoxia pathway. Histone modifications were associated with adhesion and neuron development in GBM. We identified a model with five significant genes, namely NBEAL1, AEBP1, TMEM176A, FASTK, and CD81, with prognostic efficacy. Additionally, we observed increased infiltration of T cells and CD8+ T cells in the high-risk (HR) group. 5-Fluorouracil_1073 and Taselisib_1561 were predicted as potential treatment options for GBM patients, while ABT737_1910 and Wnt_C59-1622 exhibited superior response in GBM patients of the HR group. A spike in the TP53 mutation rate was observed in the HR group. TMEM176A played a role in regulating cell proliferation and migration in vitro. We presented a novel prognostic model for patients with GBM, based on histone modification-related genes. In addition, we identified the crucial role of the TMEM176A in the regulation of GBM carcinogenic phenotypes for the first time.

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Data availability

All original data can be obtained from Yunhui Wang.

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Acknowledgements

Thanks to all the researchers who participated in this study.

Funding

The study was funded by Huzhou City Natural Science Foundation of China (Grants No. 2022YZ55).

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Authors and Affiliations

  1. Department of Neurosurgery, Deqing People’s Hospital, Deqing, Zhejiang Province, China

    Yunhui Wang, LiKang Ji & Chunfeng Ji

  2. Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Ouhai, Wenzhou, Zhejiang, 325000, China

    Fan Wang

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  1. Yunhui Wang
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  2. LiKang Ji
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  4. Fan Wang
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Contributions

YW participated in literature collection, thought construction, and article writing. LKJ and CJ participated in data collection, and FW is responsible for the full text data.

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Correspondence to Fan Wang.

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Wang, Y., Ji, L., Ji, C. et al. Multi-omics approaches establishing histone modification based prognostic model in glioma patients and further verification of the carcinogenesis mechanism. Funct Integr Genomics 23, 307 (2023). https://doi.org/10.1007/s10142-023-01229-3

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  • DOI: https://doi.org/10.1007/s10142-023-01229-3

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