Cargando…
m6A regulator-mediated methylation modification patterns and tumor microenvironment infiltration characterization in hepatocellular carcinoma
Background: There is increasing evidence of the epigenetic regulation of the immune response in cancer. However, the specific functions and mechanisms of RNA N6-methyladenosine (m6A) modification in the cell infiltration in the hepatocellular carcinoma (HCC) tumor microenvironment (TME) is unknown....
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436903/ https://www.ncbi.nlm.nih.gov/pubmed/34461607 http://dx.doi.org/10.18632/aging.203456 |
_version_ | 1783752070653804544 |
---|---|
author | Huang, Xiongpei Qiu, Zecheng Li, Liusheng Chen, Bin Huang, Peiyuan |
author_facet | Huang, Xiongpei Qiu, Zecheng Li, Liusheng Chen, Bin Huang, Peiyuan |
author_sort | Huang, Xiongpei |
collection | PubMed |
description | Background: There is increasing evidence of the epigenetic regulation of the immune response in cancer. However, the specific functions and mechanisms of RNA N6-methyladenosine (m6A) modification in the cell infiltration in the hepatocellular carcinoma (HCC) tumor microenvironment (TME) is unknown. Methods: We systematically analyzed the m6A-modification patterns of 371 HCC samples based on 23 m6A regulators, and determined their correlation with TME cell-infiltrating characteristics. Principal-component analysis algorithms was used to calculate the m6Ascore and clarify the m6A-modification patterns of individual tumors. Results: Three different m6A-modification patterns were identified in HCC, wherein the m6Acluster B and m6Acluster A had the best and worst prognosis, respectively. These three patterns had different TME cell infiltration characteristics and biological behavior. An m6A-scoring signature was constructed to evaluate the m6A-modification patterns within individual tumors. A low m6Ascore was associated with a low overall survival and high clinical stage. Moreover, the m6A-scoring signature was characterized by distinct immunotherapeutic landscapes; a high m6A score indicated a higher immune checkpoint inhibitor score in the anti-PD-1 treatment alone, anti-CTLA-4 treatment alone, or combined anti-CTLA-4/PD-1 treatment cohorts, which reflected significant treatment and clinical benefits. Conclusions: Our study highlights the significant role of the m6A modification in the HCC TME. A scoring signature to clarify the individual m6A-modification pattern would help us understand the HCC TME infiltration characterization and, thus, would guide the selection of more effective immunotherapeutic strategies. |
format | Online Article Text |
id | pubmed-8436903 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Impact Journals |
record_format | MEDLINE/PubMed |
spelling | pubmed-84369032021-09-14 m6A regulator-mediated methylation modification patterns and tumor microenvironment infiltration characterization in hepatocellular carcinoma Huang, Xiongpei Qiu, Zecheng Li, Liusheng Chen, Bin Huang, Peiyuan Aging (Albany NY) Research Paper Background: There is increasing evidence of the epigenetic regulation of the immune response in cancer. However, the specific functions and mechanisms of RNA N6-methyladenosine (m6A) modification in the cell infiltration in the hepatocellular carcinoma (HCC) tumor microenvironment (TME) is unknown. Methods: We systematically analyzed the m6A-modification patterns of 371 HCC samples based on 23 m6A regulators, and determined their correlation with TME cell-infiltrating characteristics. Principal-component analysis algorithms was used to calculate the m6Ascore and clarify the m6A-modification patterns of individual tumors. Results: Three different m6A-modification patterns were identified in HCC, wherein the m6Acluster B and m6Acluster A had the best and worst prognosis, respectively. These three patterns had different TME cell infiltration characteristics and biological behavior. An m6A-scoring signature was constructed to evaluate the m6A-modification patterns within individual tumors. A low m6Ascore was associated with a low overall survival and high clinical stage. Moreover, the m6A-scoring signature was characterized by distinct immunotherapeutic landscapes; a high m6A score indicated a higher immune checkpoint inhibitor score in the anti-PD-1 treatment alone, anti-CTLA-4 treatment alone, or combined anti-CTLA-4/PD-1 treatment cohorts, which reflected significant treatment and clinical benefits. Conclusions: Our study highlights the significant role of the m6A modification in the HCC TME. A scoring signature to clarify the individual m6A-modification pattern would help us understand the HCC TME infiltration characterization and, thus, would guide the selection of more effective immunotherapeutic strategies. Impact Journals 2021-08-30 /pmc/articles/PMC8436903/ /pubmed/34461607 http://dx.doi.org/10.18632/aging.203456 Text en Copyright: © 2021 Huang et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Huang, Xiongpei Qiu, Zecheng Li, Liusheng Chen, Bin Huang, Peiyuan m6A regulator-mediated methylation modification patterns and tumor microenvironment infiltration characterization in hepatocellular carcinoma |
title | m6A regulator-mediated methylation modification patterns and tumor microenvironment infiltration characterization in hepatocellular carcinoma |
title_full | m6A regulator-mediated methylation modification patterns and tumor microenvironment infiltration characterization in hepatocellular carcinoma |
title_fullStr | m6A regulator-mediated methylation modification patterns and tumor microenvironment infiltration characterization in hepatocellular carcinoma |
title_full_unstemmed | m6A regulator-mediated methylation modification patterns and tumor microenvironment infiltration characterization in hepatocellular carcinoma |
title_short | m6A regulator-mediated methylation modification patterns and tumor microenvironment infiltration characterization in hepatocellular carcinoma |
title_sort | m6a regulator-mediated methylation modification patterns and tumor microenvironment infiltration characterization in hepatocellular carcinoma |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436903/ https://www.ncbi.nlm.nih.gov/pubmed/34461607 http://dx.doi.org/10.18632/aging.203456 |
work_keys_str_mv | AT huangxiongpei m6aregulatormediatedmethylationmodificationpatternsandtumormicroenvironmentinfiltrationcharacterizationinhepatocellularcarcinoma AT qiuzecheng m6aregulatormediatedmethylationmodificationpatternsandtumormicroenvironmentinfiltrationcharacterizationinhepatocellularcarcinoma AT liliusheng m6aregulatormediatedmethylationmodificationpatternsandtumormicroenvironmentinfiltrationcharacterizationinhepatocellularcarcinoma AT chenbin m6aregulatormediatedmethylationmodificationpatternsandtumormicroenvironmentinfiltrationcharacterizationinhepatocellularcarcinoma AT huangpeiyuan m6aregulatormediatedmethylationmodificationpatternsandtumormicroenvironmentinfiltrationcharacterizationinhepatocellularcarcinoma |