Cargando…

EZH2 as a Prognostic Factor and Its Immune Implication with Molecular Characterization in Prostate Cancer: An Integrated Multi-Omics in Silico Analysis

Prostate cancer (PCa) is a type of potentially fatal malignant tumor. Immunotherapy has shown a lot of potential for various types of solid tumors, but the benefits have been less impressive in PCa. Enhancer of zeste homolog 2 (EZH2) is one of the three core subunits of the polycomb repressive compl...

Descripción completa

Detalles Bibliográficos
Autores principales: Du, Tian-Qi, Liu, Ruifeng, Zhang, Qiuning, Luo, Hongtao, Liu, Zhiqiang, Sun, Shilong, Wang, Xiaohu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9687944/
https://www.ncbi.nlm.nih.gov/pubmed/36358967
http://dx.doi.org/10.3390/biom12111617
_version_ 1784836141345669120
author Du, Tian-Qi
Liu, Ruifeng
Zhang, Qiuning
Luo, Hongtao
Liu, Zhiqiang
Sun, Shilong
Wang, Xiaohu
author_facet Du, Tian-Qi
Liu, Ruifeng
Zhang, Qiuning
Luo, Hongtao
Liu, Zhiqiang
Sun, Shilong
Wang, Xiaohu
author_sort Du, Tian-Qi
collection PubMed
description Prostate cancer (PCa) is a type of potentially fatal malignant tumor. Immunotherapy has shown a lot of potential for various types of solid tumors, but the benefits have been less impressive in PCa. Enhancer of zeste homolog 2 (EZH2) is one of the three core subunits of the polycomb repressive complex 2 that has histone methyltransferase activity, and the immune effects of EZH2 in PCa are still unclear. The purpose of this study was to explore the potential of EZH2 as a prognostic factor and an immune therapeutic biomarker for PCa, as well as the expression pattern and biological functions. All analyses in this study were based on publicly available databases, mainly containing Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), UCSCXenaShiny, and TISIDB. We performed differential expression analysis, developed a prognostic model, and explored potential associations between EZH2 and DNA methylation modifications, tumor microenvironment (TME), immune-related genes, tumor mutation burden (TMB), tumor neoantigen burden (TNB), and representative mismatch repair (MMR) genes. We also investigated the molecular and immunological characterizations of EZH2. Finally, we predicted immunotherapeutic responses based on EZH2 expression levels. We found that EZH2 was highly expressed in PCa, was associated with a poor prognosis, and may serve as an independent prognostic factor. EZH2 expression in PCa was associated with DNA methylation modifications, TME, immune-related genes, TMB, TNB, and MMR. By gene set enrichment analysis and gene set variation analysis, we found that multiple functions and pathways related to tumorigenesis, progression, and immune activation were enriched. Finally, we inferred that immunotherapy may be more effective for PCa patients with low EZH2 expression. In conclusion, our study showed that EZH2 could be a potentially efficient predictor of prognosis and immune response in PCa patients.
format Online
Article
Text
id pubmed-9687944
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-96879442022-11-25 EZH2 as a Prognostic Factor and Its Immune Implication with Molecular Characterization in Prostate Cancer: An Integrated Multi-Omics in Silico Analysis Du, Tian-Qi Liu, Ruifeng Zhang, Qiuning Luo, Hongtao Liu, Zhiqiang Sun, Shilong Wang, Xiaohu Biomolecules Article Prostate cancer (PCa) is a type of potentially fatal malignant tumor. Immunotherapy has shown a lot of potential for various types of solid tumors, but the benefits have been less impressive in PCa. Enhancer of zeste homolog 2 (EZH2) is one of the three core subunits of the polycomb repressive complex 2 that has histone methyltransferase activity, and the immune effects of EZH2 in PCa are still unclear. The purpose of this study was to explore the potential of EZH2 as a prognostic factor and an immune therapeutic biomarker for PCa, as well as the expression pattern and biological functions. All analyses in this study were based on publicly available databases, mainly containing Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), UCSCXenaShiny, and TISIDB. We performed differential expression analysis, developed a prognostic model, and explored potential associations between EZH2 and DNA methylation modifications, tumor microenvironment (TME), immune-related genes, tumor mutation burden (TMB), tumor neoantigen burden (TNB), and representative mismatch repair (MMR) genes. We also investigated the molecular and immunological characterizations of EZH2. Finally, we predicted immunotherapeutic responses based on EZH2 expression levels. We found that EZH2 was highly expressed in PCa, was associated with a poor prognosis, and may serve as an independent prognostic factor. EZH2 expression in PCa was associated with DNA methylation modifications, TME, immune-related genes, TMB, TNB, and MMR. By gene set enrichment analysis and gene set variation analysis, we found that multiple functions and pathways related to tumorigenesis, progression, and immune activation were enriched. Finally, we inferred that immunotherapy may be more effective for PCa patients with low EZH2 expression. In conclusion, our study showed that EZH2 could be a potentially efficient predictor of prognosis and immune response in PCa patients. MDPI 2022-11-02 /pmc/articles/PMC9687944/ /pubmed/36358967 http://dx.doi.org/10.3390/biom12111617 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Du, Tian-Qi
Liu, Ruifeng
Zhang, Qiuning
Luo, Hongtao
Liu, Zhiqiang
Sun, Shilong
Wang, Xiaohu
EZH2 as a Prognostic Factor and Its Immune Implication with Molecular Characterization in Prostate Cancer: An Integrated Multi-Omics in Silico Analysis
title EZH2 as a Prognostic Factor and Its Immune Implication with Molecular Characterization in Prostate Cancer: An Integrated Multi-Omics in Silico Analysis
title_full EZH2 as a Prognostic Factor and Its Immune Implication with Molecular Characterization in Prostate Cancer: An Integrated Multi-Omics in Silico Analysis
title_fullStr EZH2 as a Prognostic Factor and Its Immune Implication with Molecular Characterization in Prostate Cancer: An Integrated Multi-Omics in Silico Analysis
title_full_unstemmed EZH2 as a Prognostic Factor and Its Immune Implication with Molecular Characterization in Prostate Cancer: An Integrated Multi-Omics in Silico Analysis
title_short EZH2 as a Prognostic Factor and Its Immune Implication with Molecular Characterization in Prostate Cancer: An Integrated Multi-Omics in Silico Analysis
title_sort ezh2 as a prognostic factor and its immune implication with molecular characterization in prostate cancer: an integrated multi-omics in silico analysis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9687944/
https://www.ncbi.nlm.nih.gov/pubmed/36358967
http://dx.doi.org/10.3390/biom12111617
work_keys_str_mv AT dutianqi ezh2asaprognosticfactoranditsimmuneimplicationwithmolecularcharacterizationinprostatecanceranintegratedmultiomicsinsilicoanalysis
AT liuruifeng ezh2asaprognosticfactoranditsimmuneimplicationwithmolecularcharacterizationinprostatecanceranintegratedmultiomicsinsilicoanalysis
AT zhangqiuning ezh2asaprognosticfactoranditsimmuneimplicationwithmolecularcharacterizationinprostatecanceranintegratedmultiomicsinsilicoanalysis
AT luohongtao ezh2asaprognosticfactoranditsimmuneimplicationwithmolecularcharacterizationinprostatecanceranintegratedmultiomicsinsilicoanalysis
AT liuzhiqiang ezh2asaprognosticfactoranditsimmuneimplicationwithmolecularcharacterizationinprostatecanceranintegratedmultiomicsinsilicoanalysis
AT sunshilong ezh2asaprognosticfactoranditsimmuneimplicationwithmolecularcharacterizationinprostatecanceranintegratedmultiomicsinsilicoanalysis
AT wangxiaohu ezh2asaprognosticfactoranditsimmuneimplicationwithmolecularcharacterizationinprostatecanceranintegratedmultiomicsinsilicoanalysis