A pancancer analysis of histone deacetylase 3 in human tumors

Histone deacetylase 3 (HDAC3) is known to be an important role in various kinds of cancer, but its effect has not been examined on the pancancer level. Thus, a systematic pancancer analysis was conducted to explore its potential role in pancancer diagnosis, prognosis, and immune correlation research.

We used a series of databases including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) Project, The University of Alabama at Birmingham Cancer data analysis portal (UALCAN), Tumor Immune Estimation Resource (TIMER), and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), among others, to analyze the relationship between the expression of HDAC3 and the diagnosis and prognosis of cancer, the tumor microenvironment (TME), immune infiltration, tumor mutational burden (TMB), microsatellite instability (MSI), mismatch repair (MMR) system using various bioinformatics methods. Downstream pathways of HDAC3 were identified by gene set enrichment analysis (GSEA). Furthermore, the protein expression of HDAC3 in tumor tissues and normal tissues of 17 patients with gliomas was analyzed via western blotting.

The expression of HDAC3 changed in most types of tumors, which was closely related to most tumor diagnoses and negatively related to some patients' overall survival (OS) and recurrence-free survival (RFS). The pan-cancer analysis demonstrated that it was tightly correlated to DNA methylation and RNA methylation modifications and associated with TMB and MSI. The expression level of HDAC3 was positively correlated with many immune checkpoint molecules and regulators and positively associated with the infiltration levels of immune cells in the TME in most tumor types. Furthermore, enrichment analysis revealed that transcriptional misregulation in cancer and RNA splicing functions were involved in the functional mechanism of HDAC3-related genes. Experimental research showed that the protein expression of HDAC3 was elevated in tumor tissues of patients with glioma.

Through our comprehensive bioinformatics analysis, we evaluated the role of HDAC3 in pancancer, and our findings suggest that it may be an indicator for some cancer diagnoses and influence immune balance.