Aggresome-Autophagy Associated Gene HDAC6 Is a Potential Biomarker in Pan-Cancer, Especially in Colon Adenocarcinoma.

Zhiyong Zhang,Xin Zhang,Aimin Huang

doi:10.3389/fonc.2021.718589

Zhiyong Zhang, Xin Zhang + Show 1 more

Open Access

https://doi.org/10.3389/fonc.2021.718589

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Abstract

BackgroundHistone deacetylase 6 (HDAC6) regulates cytoplasmic signaling networks through the deacetylation of various cytoplasmic substrates. Recent studies have identified the role of HDAC6 in tumor development and immune metabolism, but its specific function remains unclear.MethodsThe current study determined the role of HDAC6 in tumor metabolism and tumor immunity through a multi-database pan-cancer analysis. The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Cancer Cell Line Encyclopedia (CCLE) datasets were used to determine the expression levels, prognosis, tumor progression, immune checkpoints, and immune metabolism of HDAC6 in 33 tumors. Pathways, immune checkpoints, immune neoantigens, immune microenvironment, tumor mutational burden (TMB), microsatellite instability (MSI), DNA mismatch repair (MMR), and the value of methyltransferases. The R package was used for quantitative analysis and panoramic description.ResultsIn the present study, we determined that HDAC6 is differentially expressed in pan carcinomas, and by survival, we found that HDAC6 was generally associated with the prognosis of pancreatic adenocarcinoma, Thymoma, and uveal melanoma, where low expression of HDAC6 had a significantly worse prognosis. Secondly, through this experiment, we confirmed that HDAC6 expression level was associated with tumor immune infiltration and tumor microenvironment, especially in PAAD. Finally, HDAC6 was associated with immune neoantigen and immune checkpoint gene expression profiles in all cancers in addition to TMB and MSI in pan-cancers.ConclusionHDAC6 is differentially expressed in pan-cancers and plays an essential role in tumor metabolism and immunity. HDAC6 holds promise as a tumor potential prognostic marker, especially in colon cancer.

Highlights

Living standards, dietary habits, and living environments of people is changing [1], and the incidence of various diseases is exploding [2]
The expression levels of Histone deacetylase 6 (HDAC6) in the GTEx (Figure 1A), Cell Lineage Encyclopedia (CCLE) (Figure 1B), and The Cancer Genome Atlas (TCGA) (Figure 1C) datasets were shown by a histogram
The results of the analysis showed that HDAC6 was associated with KIRP (HR = 0.940, 95CI%: 0.900–0.990, P = 0.014), THCA (HR = 1.16, 95CI%: 1.010–1.330, P = 0.038), THYM (HR = 0.820, 95CI%: 0.700–0.960, P = 0.015), and UVM (HR = 0.870, 95CI%: 0.800–0.960, P = 0.005), indicating that HDAC6 and DSS had prognostic significance (Figure 4)

Summary

Introduction

Dietary habits, and living environments of people is changing [1], and the incidence of various diseases is exploding [2]. Cancer has become a severe public health hazard; cancer incidence and mortality rates are increasing rapidly every year [3]. Breakthroughs in tumor diagnosis and tumor treatment have been made in recent years, conventional therapies, including surgery, chemotherapy, and radiation therapy, remain the first-line treatment for most cancer patients [5]. Patients with many cancers still do not achieve the desired level of 5-year survival with treatment [6]. The application of tumor biomarkers has attracted much attention from scholars, among which pan-cancer analysis has emerged as a potential option to explore new tumor biomarkers [7]. Recent studies have identified the role of HDAC6 in tumor development and immune metabolism, but its specific function remains unclear

Methods

Results

Conclusion