Comprehensive Analysis of HDAC Family Identifies as a Prognostic and Immune Infiltration Indicator and -Related Signature for Prognosis in Glioma.

The histone deacetylase (HDAC) family limited accessibility to chromatin containing tumor suppressor genes by removing acetyl groups, which was deemed a path for tumorigenesis. Considering glioma remained one of the most common brain cancers with a dichotomy prognosis and limited therapy responses, HDAC inhibitors were an area of intensive research. However, the expression profiles and prognostic value of the HDACs required more elucidation. Multiple biomedical databases were incorporated, including ONCOMINE, GEPIA, TCGA, CGGA, GEO, TIMER, cBioPortal, and Metascape, to study expression profiles, prognostic value, immune infiltration, mutation status, and enrichment of HDACs in glioma. STRING and GeneMANIA databases were used to identify -related molecules. LASSO regression, Cox regression, Kaplan-Meier plot, and receiver operating characteristic (ROC) analyses were performed for -related signature construction and validation. was significantly overexpressed in glioma, while was downregulated in glioblastoma. Except for , the HDAC family expression was significantly associated with glioma grade. Most of the HDAC family also correlated with glioma genetic mutations. Higher expression level predicted more dismal overall survival (OS) ( < 0.0001) and disease-free survival (DFS) ( < 0.0001), but a higher level of held more favorable OS ( = 2.1e-14) and DFS ( = 4.8e-08). displayed the highest mutation ratio, at 2.6% of the family. The prognostic value of was validated with ROC achieving 0.70, 0.77, 0.75, and 0.80 as separability for 1-, 3-, 5-, and 10-years OS predictions in glioma, respectively. Moreover, expression positively correlated with neutrophil (r = 0.60, = 2.88e-47) and CD4 T cell infiltration (r = 0.52, = 3.96e-35) in lower-grade glioma. The final -related signature comprised of , (Hazard Ratio:1.49, 95%Confidence Interval:1.20-1.86), , , and , and was verified by survival analysis ( < 0.0001) and ROC with 0.80, 0.84, 0.83, and 0.88 as separability for 1-, 3-, 5-, and 10-years OS predictions, respectively. The signature was enriched in chromatin binding. HDAC family was of clinical significance for glioma. Most of the HDAC family significantly correlated with the glioma grade, mutation, and codeletion. was both a prognostic and immune infiltration indicator and a central component of the -related signature for precise prognosis prediction in glioma.