Comprehensive analyses reveal the role of histone deacetylase genes in prognosis and immune response in low-grade glioma

Abstract

Many studies have shown that Histone deacetylases (HDAC) is involved in the occurrence of malignant tumors and regulates the occurrence, proliferation, invasion, and migration of malignant tumors through a variety of signaling pathways. In the present, we explored the role of Histone deacetylases genes in prognosis and immune response in low-grade glioma. Using consensus clustering, we built the new molecular clusters. Using HDAC genes, we constructed and validated the prognostic model in two independent cohort datasets. Patients were divided into high-risk and low-risk groups. Then, we explored the molecular characteristics, clinical characteristics, tumor microenvironment and immune infiltration levels of two clusters and risk groups. Receiver operating characteristic analyses were built for model assessment. We finally detected the expression levels of signature genes between tumor and normal tissues. Low-grade can be separated into two molecular clusters using 11 HDACs genes. Two clusters had different clinical characteristics and prognosis. Nex, we constructed a prognosis model using six HDAC genes (HDAC1, HDAC4, HDAC5, HDAC7, HDAC9, and HDAC10), which was also validated in an independent cohort dataset. Furthermore, multivariate cox regression indicated that the calculated risk score was independently associated with prognosis in low-grade glioma, and risk score can predict the five-year survival probability of low-grade glioma 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, using signature genes, we identified several small molecular compounds that could be useful for low-grade glioma patients’ treatment. Finally, we detected the expression levels of signature genes in tumor tissues. our study uncovers the biology function role of HDAC genes in low-grade glioma. We identified new molecular subtypes and established a prognostic model based on six HDAC genes, which was well applied in two independent cohort data. The regulation of HDAC genes in low-grade glioma involved in multiple molecular function and signaling pathways and immune infiltration levels. Further experiments in vivo and vitro were required to confirm the present findings.