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The Prognostic and Therapeutic Role of Histone Acetylation Modification in LIHC Development and Progression

Background and Objectives: The modification of histone acetylation plays a vital role in regulating tumor occurrence and development, but the interaction between histone acetylation modulator genes and the liver hepatocellular carcinoma (LIHC) microenvironment, as well as immunotherapy, has not been...

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Autores principales: Gao, Ji, Han, Sheng, Gu, Jian, Wu, Chen, Mu, Xiaoxin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10536947/
https://www.ncbi.nlm.nih.gov/pubmed/37763801
http://dx.doi.org/10.3390/medicina59091682
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author Gao, Ji
Han, Sheng
Gu, Jian
Wu, Chen
Mu, Xiaoxin
author_facet Gao, Ji
Han, Sheng
Gu, Jian
Wu, Chen
Mu, Xiaoxin
author_sort Gao, Ji
collection PubMed
description Background and Objectives: The modification of histone acetylation plays a vital role in regulating tumor occurrence and development, but the interaction between histone acetylation modulator genes and the liver hepatocellular carcinoma (LIHC) microenvironment, as well as immunotherapy, has not been investigated. Materials and Methods: Analysis of all statistical data was carried out using R software (Version 4.2.0) and the online tool Sangerbox. Comprehensive bioinformatics analysis, including signature construction and validation, functional analyses, immune and genomic features analyses, and immunotherapy prediction analyses, were performed to explore the prognostic and therapeutic role of histone acetylation modulator genes in LIHC development and progression. Results: The LIHC cohort from The Cancer Genome Atlas (TCGA) database was selected as the training cohort; the GSE76427 cohort from the Gene Expression Omnibus (GEO) database and the LIRI-JP cohort from the International Cancer Genome Consortium (ICGC) database were selected as the validation cohorts. The histone acetylation modulator gene-based prognostic signature was constructed and validated successfully. Immune infiltration analysis showed that most immune cells and immune functions were enriched in patients with high histone acetylation risk scores (HARS). Additionally, high levels of checkpoint inhibitors (ICIs) and human leukocyte antigens (HLAs) were also observed in high HARS patients. Meanwhile, TIDE algorithm analysis was conducted to explore the relationship between HARS and immunotherapy response, and submap algorithm analysis was used for the verification of the results, from which we found that high HAPS patients were more likely to respond to immunotherapy. Conclusions: Our findings revealed that the histone acetylation modulator genes, particularly for KAT21, SIRT6, and HAT1, may have the potential to function as a new prognostic marker and therapeutic target for LIHC.
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spelling pubmed-105369472023-09-29 The Prognostic and Therapeutic Role of Histone Acetylation Modification in LIHC Development and Progression Gao, Ji Han, Sheng Gu, Jian Wu, Chen Mu, Xiaoxin Medicina (Kaunas) Article Background and Objectives: The modification of histone acetylation plays a vital role in regulating tumor occurrence and development, but the interaction between histone acetylation modulator genes and the liver hepatocellular carcinoma (LIHC) microenvironment, as well as immunotherapy, has not been investigated. Materials and Methods: Analysis of all statistical data was carried out using R software (Version 4.2.0) and the online tool Sangerbox. Comprehensive bioinformatics analysis, including signature construction and validation, functional analyses, immune and genomic features analyses, and immunotherapy prediction analyses, were performed to explore the prognostic and therapeutic role of histone acetylation modulator genes in LIHC development and progression. Results: The LIHC cohort from The Cancer Genome Atlas (TCGA) database was selected as the training cohort; the GSE76427 cohort from the Gene Expression Omnibus (GEO) database and the LIRI-JP cohort from the International Cancer Genome Consortium (ICGC) database were selected as the validation cohorts. The histone acetylation modulator gene-based prognostic signature was constructed and validated successfully. Immune infiltration analysis showed that most immune cells and immune functions were enriched in patients with high histone acetylation risk scores (HARS). Additionally, high levels of checkpoint inhibitors (ICIs) and human leukocyte antigens (HLAs) were also observed in high HARS patients. Meanwhile, TIDE algorithm analysis was conducted to explore the relationship between HARS and immunotherapy response, and submap algorithm analysis was used for the verification of the results, from which we found that high HAPS patients were more likely to respond to immunotherapy. Conclusions: Our findings revealed that the histone acetylation modulator genes, particularly for KAT21, SIRT6, and HAT1, may have the potential to function as a new prognostic marker and therapeutic target for LIHC. MDPI 2023-09-18 /pmc/articles/PMC10536947/ /pubmed/37763801 http://dx.doi.org/10.3390/medicina59091682 Text en © 2023 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
Gao, Ji
Han, Sheng
Gu, Jian
Wu, Chen
Mu, Xiaoxin
The Prognostic and Therapeutic Role of Histone Acetylation Modification in LIHC Development and Progression
title The Prognostic and Therapeutic Role of Histone Acetylation Modification in LIHC Development and Progression
title_full The Prognostic and Therapeutic Role of Histone Acetylation Modification in LIHC Development and Progression
title_fullStr The Prognostic and Therapeutic Role of Histone Acetylation Modification in LIHC Development and Progression
title_full_unstemmed The Prognostic and Therapeutic Role of Histone Acetylation Modification in LIHC Development and Progression
title_short The Prognostic and Therapeutic Role of Histone Acetylation Modification in LIHC Development and Progression
title_sort prognostic and therapeutic role of histone acetylation modification in lihc development and progression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10536947/
https://www.ncbi.nlm.nih.gov/pubmed/37763801
http://dx.doi.org/10.3390/medicina59091682
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