The Prognostic and Therapeutic Role of Histone Acetylation Modification in LIHC Development and Progression
<i>Background and Objectives:</i> 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 immunoth...
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| Format: | Article |
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MDPI AG
2023-09-01
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| Series: | Medicina |
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| Online Access: | https://www.mdpi.com/1648-9144/59/9/1682 |
| _version_ | 1797578883895132160 |
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| author | Ji Gao Sheng Han Jian Gu Chen Wu Xiaoxin Mu |
| author_facet | Ji Gao Sheng Han Jian Gu Chen Wu Xiaoxin Mu |
| author_sort | Ji Gao |
| collection | DOAJ |
| description | <i>Background and Objectives:</i> 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. <i>Materials and Methods:</i> 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. <i>Results:</i> 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. <i>Conclusions:</i> 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. |
| first_indexed | 2024-03-10T22:29:03Z |
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| issn | 1010-660X 1648-9144 |
| language | English |
| last_indexed | 2024-03-10T22:29:03Z |
| publishDate | 2023-09-01 |
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| series | Medicina |
| spelling | doaj.art-6ce66229678948a0941220de48be4c762023-11-19T11:53:24ZengMDPI AGMedicina1010-660X1648-91442023-09-01599168210.3390/medicina59091682The Prognostic and Therapeutic Role of Histone Acetylation Modification in LIHC Development and ProgressionJi Gao0Sheng Han1Jian Gu2Chen Wu3Xiaoxin Mu4Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, ChinaHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, ChinaHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, ChinaHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, ChinaHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China<i>Background and Objectives:</i> 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. <i>Materials and Methods:</i> 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. <i>Results:</i> 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. <i>Conclusions:</i> 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.https://www.mdpi.com/1648-9144/59/9/1682histone acetylationLIHCtumor microenvironmentimmunotherapysignature |
| spellingShingle | Ji Gao Sheng Han Jian Gu Chen Wu Xiaoxin Mu The Prognostic and Therapeutic Role of Histone Acetylation Modification in LIHC Development and Progression Medicina histone acetylation LIHC tumor microenvironment immunotherapy signature |
| 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 | histone acetylation LIHC tumor microenvironment immunotherapy signature |
| url | https://www.mdpi.com/1648-9144/59/9/1682 |
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