Cargando…

Identification of New m(6)A Methylation Modification Patterns and Tumor Microenvironment Infiltration Landscape that Predict Clinical Outcomes for Papillary Renal Cell Carcinoma Patients

N6-methyladenosine (m(6)A) is the product of the most prevalent mRNA modification in eukaryotic cells. Accumulating evidence shows that tumor microenvironment (TME) plays a pivotal role in tumor development. However, the underlying relationship between m(6)A modification and the TME of a papillary r...

Descripción completa

Detalles Bibliográficos
Autores principales: Zheng, Bin, Cheng, Fajuan, Yao, Zhongshun, Zhang, Yiming, Cong, Zixiang, Wang, Jianwei, Niu, Zhihong, He, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8968637/
https://www.ncbi.nlm.nih.gov/pubmed/35372339
http://dx.doi.org/10.3389/fcell.2022.818194
_version_ 1784679088975249408
author Zheng, Bin
Cheng, Fajuan
Yao, Zhongshun
Zhang, Yiming
Cong, Zixiang
Wang, Jianwei
Niu, Zhihong
He, Wei
author_facet Zheng, Bin
Cheng, Fajuan
Yao, Zhongshun
Zhang, Yiming
Cong, Zixiang
Wang, Jianwei
Niu, Zhihong
He, Wei
author_sort Zheng, Bin
collection PubMed
description N6-methyladenosine (m(6)A) is the product of the most prevalent mRNA modification in eukaryotic cells. Accumulating evidence shows that tumor microenvironment (TME) plays a pivotal role in tumor development. However, the underlying relationship between m(6)A modification and the TME of a papillary renal cell carcinoma (PRCC) is still unclear. To investigate the relationship between m(6)A modification and prognosis and immunotherapeutic efficacy for PRCC, we looked for distinct m(6)A modification patterns based on 23 m(6)A-related genes. Next, the correlation between m(6)A modification patterns and TME-related characteristics was investigated. Then, the intersected differentially expressed genes were selected and the scoring system, denoted as m(6)A score, was established to evaluate m(6)A modification, prognosis, and immunotherapeutic efficacy. In this study, three distinct m(6)A expression clusters were identified. Based on the results of immune cell infiltration analysis and functional analysis, carcinogenic pathways, TME-related immune cells, and pathways were identified as well. More importantly, the established m(6)A score showed good value in predicting clinical outcomes according to results using external cohorts. Specifically, PRCC patients with low m(6)A score value showed better survival, immunotherapeutic response, and higher tumor mutation burden. Furthermore, immunohistochemistry using PRCC clinical samples from our medical center was carried out and verified our results. In conclusion, this study highlights the underlying correlation between m(6)A modification and the immune landscape and, hence, enhances our understanding of the TME and improved the therapeutic outlook for PRCC patients.
format Online
Article
Text
id pubmed-8968637
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-89686372022-04-01 Identification of New m(6)A Methylation Modification Patterns and Tumor Microenvironment Infiltration Landscape that Predict Clinical Outcomes for Papillary Renal Cell Carcinoma Patients Zheng, Bin Cheng, Fajuan Yao, Zhongshun Zhang, Yiming Cong, Zixiang Wang, Jianwei Niu, Zhihong He, Wei Front Cell Dev Biol Cell and Developmental Biology N6-methyladenosine (m(6)A) is the product of the most prevalent mRNA modification in eukaryotic cells. Accumulating evidence shows that tumor microenvironment (TME) plays a pivotal role in tumor development. However, the underlying relationship between m(6)A modification and the TME of a papillary renal cell carcinoma (PRCC) is still unclear. To investigate the relationship between m(6)A modification and prognosis and immunotherapeutic efficacy for PRCC, we looked for distinct m(6)A modification patterns based on 23 m(6)A-related genes. Next, the correlation between m(6)A modification patterns and TME-related characteristics was investigated. Then, the intersected differentially expressed genes were selected and the scoring system, denoted as m(6)A score, was established to evaluate m(6)A modification, prognosis, and immunotherapeutic efficacy. In this study, three distinct m(6)A expression clusters were identified. Based on the results of immune cell infiltration analysis and functional analysis, carcinogenic pathways, TME-related immune cells, and pathways were identified as well. More importantly, the established m(6)A score showed good value in predicting clinical outcomes according to results using external cohorts. Specifically, PRCC patients with low m(6)A score value showed better survival, immunotherapeutic response, and higher tumor mutation burden. Furthermore, immunohistochemistry using PRCC clinical samples from our medical center was carried out and verified our results. In conclusion, this study highlights the underlying correlation between m(6)A modification and the immune landscape and, hence, enhances our understanding of the TME and improved the therapeutic outlook for PRCC patients. Frontiers Media S.A. 2022-03-17 /pmc/articles/PMC8968637/ /pubmed/35372339 http://dx.doi.org/10.3389/fcell.2022.818194 Text en Copyright © 2022 Zheng, Cheng, Yao, Zhang, Cong, Wang, Niu and He. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Zheng, Bin
Cheng, Fajuan
Yao, Zhongshun
Zhang, Yiming
Cong, Zixiang
Wang, Jianwei
Niu, Zhihong
He, Wei
Identification of New m(6)A Methylation Modification Patterns and Tumor Microenvironment Infiltration Landscape that Predict Clinical Outcomes for Papillary Renal Cell Carcinoma Patients
title Identification of New m(6)A Methylation Modification Patterns and Tumor Microenvironment Infiltration Landscape that Predict Clinical Outcomes for Papillary Renal Cell Carcinoma Patients
title_full Identification of New m(6)A Methylation Modification Patterns and Tumor Microenvironment Infiltration Landscape that Predict Clinical Outcomes for Papillary Renal Cell Carcinoma Patients
title_fullStr Identification of New m(6)A Methylation Modification Patterns and Tumor Microenvironment Infiltration Landscape that Predict Clinical Outcomes for Papillary Renal Cell Carcinoma Patients
title_full_unstemmed Identification of New m(6)A Methylation Modification Patterns and Tumor Microenvironment Infiltration Landscape that Predict Clinical Outcomes for Papillary Renal Cell Carcinoma Patients
title_short Identification of New m(6)A Methylation Modification Patterns and Tumor Microenvironment Infiltration Landscape that Predict Clinical Outcomes for Papillary Renal Cell Carcinoma Patients
title_sort identification of new m(6)a methylation modification patterns and tumor microenvironment infiltration landscape that predict clinical outcomes for papillary renal cell carcinoma patients
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8968637/
https://www.ncbi.nlm.nih.gov/pubmed/35372339
http://dx.doi.org/10.3389/fcell.2022.818194
work_keys_str_mv AT zhengbin identificationofnewm6amethylationmodificationpatternsandtumormicroenvironmentinfiltrationlandscapethatpredictclinicaloutcomesforpapillaryrenalcellcarcinomapatients
AT chengfajuan identificationofnewm6amethylationmodificationpatternsandtumormicroenvironmentinfiltrationlandscapethatpredictclinicaloutcomesforpapillaryrenalcellcarcinomapatients
AT yaozhongshun identificationofnewm6amethylationmodificationpatternsandtumormicroenvironmentinfiltrationlandscapethatpredictclinicaloutcomesforpapillaryrenalcellcarcinomapatients
AT zhangyiming identificationofnewm6amethylationmodificationpatternsandtumormicroenvironmentinfiltrationlandscapethatpredictclinicaloutcomesforpapillaryrenalcellcarcinomapatients
AT congzixiang identificationofnewm6amethylationmodificationpatternsandtumormicroenvironmentinfiltrationlandscapethatpredictclinicaloutcomesforpapillaryrenalcellcarcinomapatients
AT wangjianwei identificationofnewm6amethylationmodificationpatternsandtumormicroenvironmentinfiltrationlandscapethatpredictclinicaloutcomesforpapillaryrenalcellcarcinomapatients
AT niuzhihong identificationofnewm6amethylationmodificationpatternsandtumormicroenvironmentinfiltrationlandscapethatpredictclinicaloutcomesforpapillaryrenalcellcarcinomapatients
AT hewei identificationofnewm6amethylationmodificationpatternsandtumormicroenvironmentinfiltrationlandscapethatpredictclinicaloutcomesforpapillaryrenalcellcarcinomapatients