H4-methylation regulators mediated epitranscriptome patterns and tumor microenvironment infiltration characterization in hepatocellular carcinoma
Abstract Epigenetic modifications are involved in the remodeling of the tumor microenvironment (TME) and the regulation of immune response. Nonetheless, the role of histone H4 methylation (H4M) modification in the TME and immune regulation of hepatocellular carcinoma (HCC) is unknown. As a result, t...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-03-01
|
| Series: | Clinical Epigenetics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13148-023-01460-6 |
| _version_ | 1797864325665259520 |
|---|---|
| author | Linyuan Yu Tao Ji Wei Liao Yuyan Xu Yinghao Fang Qing Zhu Jianmin Nie Dinghua Yang |
| author_facet | Linyuan Yu Tao Ji Wei Liao Yuyan Xu Yinghao Fang Qing Zhu Jianmin Nie Dinghua Yang |
| author_sort | Linyuan Yu |
| collection | DOAJ |
| description | Abstract Epigenetic modifications are involved in the remodeling of the tumor microenvironment (TME) and the regulation of immune response. Nonetheless, the role of histone H4 methylation (H4M) modification in the TME and immune regulation of hepatocellular carcinoma (HCC) is unknown. As a result, the purpose of this research is to discover H4M-mediated modification patterns and their effects on TME and immunologic characteristics in HCC. A total of 2305 samples were enrolled from 13 different cohorts. With the help of consensus clustering analysis, three distinct H4M modification patterns were identified. The cell-infiltrating characteristics of TME under these three patterns were highly consistent with their enriched biological processes and clinical outcome. The H4Mscore was then created using principal component analysis algorithm to quantify the H4M modification pattern of each individual tumor and was systematically correlated with representative tumor characteristics. We found that analyzing H4M modification patterns within individual tumors could predict TME infiltration, homologous recombination deficiency (HRD), intratumor heterogeneity, proliferation activity, mRNA stemness index, and prognosis. The group with a low H4Mscore had an inflamed TME phenotype and a better immunotherapy response, as well as a better survival outcome. The prognostic value of H4Mscore was validated in three internal cohorts and five external cohorts, respectively. In external immunotherapy cohorts, the low H4Mscore was also linked to an enhanced response to anti-PD-1/L1 and anti-CTLA4 immunotherapy and a better prognosis. This study revealed that H4M modification played an important role in forming TME diversity and complexity. Evaluating the H4M modification pattern of individual tumors could help us learn more about TME and develop more effective immunotherapy strategies. |
| first_indexed | 2024-04-09T22:51:03Z |
| format | Article |
| id | doaj.art-007d7bcd19fa493e857fdbf44b92c178 |
| institution | Directory Open Access Journal |
| issn | 1868-7083 |
| language | English |
| last_indexed | 2024-04-09T22:51:03Z |
| publishDate | 2023-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Clinical Epigenetics |
| spelling | doaj.art-007d7bcd19fa493e857fdbf44b92c1782023-03-22T11:37:29ZengBMCClinical Epigenetics1868-70832023-03-0115112010.1186/s13148-023-01460-6H4-methylation regulators mediated epitranscriptome patterns and tumor microenvironment infiltration characterization in hepatocellular carcinomaLinyuan Yu0Tao Ji1Wei Liao2Yuyan Xu3Yinghao Fang4Qing Zhu5Jianmin Nie6Dinghua Yang7Unit of Hepatobiliary Surgery, Department of General Surgery, Nanfang Hospital, Southern Medical UniversityUnit of Hepatobiliary Surgery, Department of General Surgery, Nanfang Hospital, Southern Medical UniversityUnit of Hepatobiliary Surgery, Department of General Surgery, Nanfang Hospital, Southern Medical UniversityGeneral Surgery Center, Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical UniversityUnit of Hepatobiliary Surgery, Department of General Surgery, Nanfang Hospital, Southern Medical UniversityUnit of Hepatobiliary Surgery, Department of General Surgery, Nanfang Hospital, Southern Medical UniversityUnit of Hepatobiliary Surgery, Department of General Surgery, Nanfang Hospital, Southern Medical UniversityUnit of Hepatobiliary Surgery, Department of General Surgery, Nanfang Hospital, Southern Medical UniversityAbstract Epigenetic modifications are involved in the remodeling of the tumor microenvironment (TME) and the regulation of immune response. Nonetheless, the role of histone H4 methylation (H4M) modification in the TME and immune regulation of hepatocellular carcinoma (HCC) is unknown. As a result, the purpose of this research is to discover H4M-mediated modification patterns and their effects on TME and immunologic characteristics in HCC. A total of 2305 samples were enrolled from 13 different cohorts. With the help of consensus clustering analysis, three distinct H4M modification patterns were identified. The cell-infiltrating characteristics of TME under these three patterns were highly consistent with their enriched biological processes and clinical outcome. The H4Mscore was then created using principal component analysis algorithm to quantify the H4M modification pattern of each individual tumor and was systematically correlated with representative tumor characteristics. We found that analyzing H4M modification patterns within individual tumors could predict TME infiltration, homologous recombination deficiency (HRD), intratumor heterogeneity, proliferation activity, mRNA stemness index, and prognosis. The group with a low H4Mscore had an inflamed TME phenotype and a better immunotherapy response, as well as a better survival outcome. The prognostic value of H4Mscore was validated in three internal cohorts and five external cohorts, respectively. In external immunotherapy cohorts, the low H4Mscore was also linked to an enhanced response to anti-PD-1/L1 and anti-CTLA4 immunotherapy and a better prognosis. This study revealed that H4M modification played an important role in forming TME diversity and complexity. Evaluating the H4M modification pattern of individual tumors could help us learn more about TME and develop more effective immunotherapy strategies.https://doi.org/10.1186/s13148-023-01460-6Histone H4 methylationHepatocellular carcinomaMolecular subtypeTumor microenvironmentImmunotherapy biomarker |
| spellingShingle | Linyuan Yu Tao Ji Wei Liao Yuyan Xu Yinghao Fang Qing Zhu Jianmin Nie Dinghua Yang H4-methylation regulators mediated epitranscriptome patterns and tumor microenvironment infiltration characterization in hepatocellular carcinoma Clinical Epigenetics Histone H4 methylation Hepatocellular carcinoma Molecular subtype Tumor microenvironment Immunotherapy biomarker |
| title | H4-methylation regulators mediated epitranscriptome patterns and tumor microenvironment infiltration characterization in hepatocellular carcinoma |
| title_full | H4-methylation regulators mediated epitranscriptome patterns and tumor microenvironment infiltration characterization in hepatocellular carcinoma |
| title_fullStr | H4-methylation regulators mediated epitranscriptome patterns and tumor microenvironment infiltration characterization in hepatocellular carcinoma |
| title_full_unstemmed | H4-methylation regulators mediated epitranscriptome patterns and tumor microenvironment infiltration characterization in hepatocellular carcinoma |
| title_short | H4-methylation regulators mediated epitranscriptome patterns and tumor microenvironment infiltration characterization in hepatocellular carcinoma |
| title_sort | h4 methylation regulators mediated epitranscriptome patterns and tumor microenvironment infiltration characterization in hepatocellular carcinoma |
| topic | Histone H4 methylation Hepatocellular carcinoma Molecular subtype Tumor microenvironment Immunotherapy biomarker |
| url | https://doi.org/10.1186/s13148-023-01460-6 |
| work_keys_str_mv | AT linyuanyu h4methylationregulatorsmediatedepitranscriptomepatternsandtumormicroenvironmentinfiltrationcharacterizationinhepatocellularcarcinoma AT taoji h4methylationregulatorsmediatedepitranscriptomepatternsandtumormicroenvironmentinfiltrationcharacterizationinhepatocellularcarcinoma AT weiliao h4methylationregulatorsmediatedepitranscriptomepatternsandtumormicroenvironmentinfiltrationcharacterizationinhepatocellularcarcinoma AT yuyanxu h4methylationregulatorsmediatedepitranscriptomepatternsandtumormicroenvironmentinfiltrationcharacterizationinhepatocellularcarcinoma AT yinghaofang h4methylationregulatorsmediatedepitranscriptomepatternsandtumormicroenvironmentinfiltrationcharacterizationinhepatocellularcarcinoma AT qingzhu h4methylationregulatorsmediatedepitranscriptomepatternsandtumormicroenvironmentinfiltrationcharacterizationinhepatocellularcarcinoma AT jianminnie h4methylationregulatorsmediatedepitranscriptomepatternsandtumormicroenvironmentinfiltrationcharacterizationinhepatocellularcarcinoma AT dinghuayang h4methylationregulatorsmediatedepitranscriptomepatternsandtumormicroenvironmentinfiltrationcharacterizationinhepatocellularcarcinoma |