Comprehensive analysis of Histone deacetylases genes in the prognosis and immune infiltration of glioma patients

Abstract

AbstractThe occurrence and development of tumors are closely related to histone deacetylases (HDACs). However, the overall biology and prognosis are still unknown in glioma. In the present study, we comprehensively explored the biology function and prognosis of eleven HDAC genes in glioma, which may contribute the more understanding of molecular mechanisms and potential therapeutic targets for glioma patients.We systematically described the expression files, molecular subtypes, prognostic value, immune filtration and tumor microenvironment and gene alteration, function and pathways enrichment, and drug sensitivity using TCGA and CGGA datasets. We developed and validated the prognostic model based on HDACs genes in glioma using LASSO, univariate, and multivariate cox regression. Receiver operating characteristic analyses were used for model evaluating. We also validated the expressions of HDACs genes included in the model in non-tumor and glioma tissues samples. Glioma patients can be divided into two subclasses based on eleven HDAC genes, and patients from two subclasses had markedly different survival outcomes. Then, using six HDAC genes (HDAC1, HDAC3, HDAC4, HDAC5, HDAC7, and HDAC9), we established a prognostic model in glioma patients, and this prognostic model was well validated in an independent cohort population. Furthermore, the calculated risk score from six HDACA genes expression was suggested to be an independent prognostic factor, which can predict the five-year overall survival of glioma patients well. High-risk patients can be attributed to multiple complex function and molecular signaling pathways, and the genes alterations of high- and low-risk patients were significantly different. We also found that different survival outcomes of high- and low-risk patients could be involved in the differences of immune filtration level and tumor microenvironment. Subsequently, we identified several small molecular compounds that could be favorable for glioma patients’ treatment. And finally, the expression levels of HDAC genes from prognostic model were validated in glioma and non-tumor tissues samples.Our results revealed the clinical utility and potential molecular mechanisms of HDAC genes in glioma. Model based on six HDAC genes can predict the overall survival of glioma patients well, which can be served as potential therapeutic targets.