Prognosis and immunological characteristics of HDAC family in pan-cancer through integrative multi-omic analysis

Changsheng Chen; KE WANG; Yu Zhang; Yixin Qi; Chong Shen; Zhe Zhang; Zongliang Zhang; Han Yang; Hailong Hu

doi:10.1186/s43042-024-00518-1

journal article Open Access Mar 30, 2024

Prognosis and immunological characteristics of HDAC family in pan-cancer through integrative multi-omic analysis

Changsheng Chen

Yixin Qi Chong Shen

Egyptian Journal of Medical Human Genetics Vol. 25 No. 1 · Springer Science and Business Media LLC

View at Publisher Save 10.1186/s43042-024-00518-1

Abstract

Abstract
Background
The histone deacetylase (HDAC) family plays a significant role in a variety of biological processes related to cancer, such as metabolism and cancer progression, and recognized as a target of anti-cancer drugs. Nevertheless, there has been limited systematic research available regarding HDAC family in human cancers using multi-omics approaches.

Objective
To evaluate the prognostic implications and immunological features of the HDAC family across multiple cancer types through comprehensive multi-omics analysis.

Methods
We studied the associations of HDAC activity and a variety of factors, encompassing immune checkpoint genes, the tumor microenvironment (TME), instability of microsatellites (MSI), inherited mutations, variation in copy number, tumor mutation burden (TMB), and sensitivity to drugs in a variety of cancer types. Moreover, we analyzed the link between the degree of HDAC activity and the effectiveness of immunotherapy in several cohorts, providing significant details about the possible impact of HDACs on immunotherapeutic responses. Furthermore, we explored potential signaling pathways of HDACs in bladder cancer (BC) using gene set enrichment analysis (GSEA). Immune infiltration analysis in bladder cancer was performed based on HDACs expression, copy number or somatic mutations. Furthermore, the Human Protein Atlas (HPA) dataset has been used to validate the expression of the HDACs protein in BC.

Results
The HDACs expression exhibits significant heterogeneity across different cancer types and is significantly correlated with patient prognosis, clinical traits, mutations, TME, TMB, MSI, immune checkpoint genes, and objective responses in immunotherapy. The drug sensitivity of cancers was found to be correlated with the gene expression of specific HDAC familial members. In BC, GSEA demonstrates enrichment of multiple immune-related functions and pathways; moreover, there are significant associations between genomic variations in HDACs and the degree of typical immunological cell recruitment. Furthermore, findings from differential expression analysis in BC are validated by protein expression analysis obtained from the HPA database.

Conclusions
These findings reveal the significance of HDAC family in survival prognosis and treatment guidance of human cancers, and some of them have the potential to be used as immunotherapy biomarkers.

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Details

Published: Mar 30, 2024
Vol/Issue: 25(1)
License: View

Authors

Department of Computer Science, Columbia University, 475 Riverside Dr., Mail Code 7717, New York, NY 10115, USA

Y

Yu Zhang

Howard Hughes Medical Institute, Waksman Institute, and Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, NJ 08854, USA.

Key Laboratory of Biomass Chemical Engineering (Education Ministry), College of Chemical and Biological Engineering Zhejiang University Hangzhou Zhejiang China

Funding

The Tianjin Municipal Health Industry Key Project Award: TJWJ2022XK014

Technology Project of Tianjin Binhai New Area Health Commission Award: 2019BWKY026

Tianjin Institute of Urology Talent Funding Program Award: MYSRC202310

Scientific Research Project of Tianjin Municipal Education Commission Award: 2022ZD069

Cite This Article

Changsheng Chen, KE WANG, Yu Zhang, et al. (2024). Prognosis and immunological characteristics of HDAC family in pan-cancer through integrative multi-omic analysis. Egyptian Journal of Medical Human Genetics, 25(1). https://doi.org/10.1186/s43042-024-00518-1

Prognosis and immunological characteristics of HDAC family in pan-cancer through integrative multi-omic analysis

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