Abstract
Gliomas are the most common and aggressive malignancies of the central nervous system. Histone deacetylases (HDACs) are important targets in cancer treatment. They regulate complex cellular mechanisms that influence tumor biology and immunogenicity. However, little is known about the function of HDACs in glioma. The Oncomine, Human Protein Atlas, Gene Expression Profiling Interactive Analysis, Broad Institute Cancer Cell Line Encyclopedia, Chinese Glioma Genome Atlas, OmicShare, cBioPortal, GeneMANIA, STRING, and TIMER databases were utilized to analyze the differential expression, prognostic value, and genetic alteration of HDAC and immune cell infiltration in patients with glioma. HDAC1/2 were considerable upregulated whereas HDAC11 was significantly downregulated in cancer tissues. HDAC1/2/3/4/5/7/8/11 were significantly correlated with the clinical glioma stage. HDAC1/2/3/10 were strongly upregulated in 11 glioma cell lines. High HDCA1/3/7 and low HDAC4/5/11 mRNA levels were significantly associated with overall survival and disease-free survival in glioma. HDAC1/2/3/4/5/7/9/10/11 are potential useful biomarkers for predicting the survival of patients with glioma. The functions of HDACs and 50 neighboring genes were primarily related to transcriptional dysregulation in cancers and the Notch, cGMP-PKG, and thyroid hormone signaling pathways. HDAC expression was significantly correlated with the infiltration of B cells, CD4+ T cells, CD8+ T cells, macrophages, neutrophils, and dendritic cells in glioma. Our study indicated that HDACs are putative precision therapy targets and prognostic biomarkers of survival in glioma patients.
Highlights
Glioma is the most common tumor of the central nervous system (CNS)
The Cancer Genome Atlas (TCGA) statistics revealed that HDAC1 expression was 3.131-fold higher (p = 3.08E-8) in ductal brain glioblastoma than in normal tissues (Table 1)
Most of the current clinical trials are phase I/II clinical trials, and further phase III trials are needed to demonstrate the role of histone acetylases in gliomas
Summary
Glioma is the most common tumor of the central nervous system (CNS). It accounts for 30% of all CNS tumors and 80% of all malignant brain tumors (Ostrom et al, 2019). Progress has been made in glioblastoma (GBM) treatment by combining maximal surgical resection with radiotherapy and concurrent and adjuvant temozolomide chemotherapy. The two- and fiveyear survival rates are only 25 and 10%, respectively, (Stupp et al, 2005; Stupp et al, 2009). Tumor heterogeneity is a major challenge in precise glioma diagnosis and therapy (Neftel et al, 2019). Molecular signatures for glioma are urgently required (Song et al, 2014)
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