Comprehensive Analysis of m6A RNA Methylation Regulators and the Immune Microenvironment to Aid Immunotherapy in Pancreatic Cancer

Pancreatic cancer (PAAD) is one of the most malignant cancers and immune microenvironment has been proved to be involved in pathogenesis of PAAD. m6A modification, related to the expression of m6A regulators, participates in the development of multiple cancers. However, the correlation between m6A r...

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Autores principales: Yongdong Guo, Ronglin Wang, Junqiang Li, Yang Song, Jie Min, Ting Zhao, Lei Hua, Jingjie Shi, Chao Zhang, Peixiang Ma, Cheng Yang, Liaoliao Zhu, Dongxue Gan, Shanshan Li, Xiaonan Liu, Haichuan Su
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Publicado: Frontiers Media S.A. 2021
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spelling oai:doaj.org-article:641549c322a343b08db58d183c9c64762021-11-05T14:46:18ZComprehensive Analysis of m6A RNA Methylation Regulators and the Immune Microenvironment to Aid Immunotherapy in Pancreatic Cancer1664-322410.3389/fimmu.2021.769425https://doaj.org/article/641549c322a343b08db58d183c9c64762021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.769425/fullhttps://doaj.org/toc/1664-3224Pancreatic cancer (PAAD) is one of the most malignant cancers and immune microenvironment has been proved to be involved in pathogenesis of PAAD. m6A modification, related to the expression of m6A regulators, participates in the development of multiple cancers. However, the correlation between m6A regulators and immune microenvironment was largely unknown in PAAD. And because of the small sample size of pancreatic cancer in the TCGA database, it is not enough to draw a convincing conclusion. In the present study, we downloaded seven pancreatic cancer datasets with survival data and removed batch effects among these datasets to be used as the PAAD cohort to analyze the immune landscape of PAAD and the expression pattern of m6A regulators and divided the integrated dataset into cluster 1 and cluster 2 by consensus clustering for m6A regulators. Lower m6A regulators were found to be related to higher immune cell infiltration and a better survival. Moreover, we identified six m6A regulators and constructed the prognostic signature of m6A regulators. Patients with low-risk score had a higher response to immune checkpoint inhibitor and a longer overall survival. To figure out the underlying mechanism, we analyzed the cancer immunity cycle, most altered genes, gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) in risk subtypes. In summary, the present study proved m6A regulators modulated the PAAD immune microenvironment. And risk scores served as predictive indicator for immunotherapy and played a prognostic role for PAAD patients. Our study provided novel therapeutic targets to improve immunotherapy efficacy.Yongdong GuoRonglin WangJunqiang LiYang SongJie MinTing ZhaoLei HuaJingjie ShiChao ZhangPeixiang MaCheng YangLiaoliao ZhuDongxue GanShanshan LiXiaonan LiuHaichuan SuFrontiers Media S.A.articlepancreatic cancerm6A regulatorsimmune microenvironmentimmunotherapyprognosisImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution DOAJ
collection DOAJ
language EN
topic pancreatic cancer
m6A regulators
immune microenvironment
immunotherapy
prognosis
Immunologic diseases. Allergy
RC581-607
spellingShingle pancreatic cancer
m6A regulators
immune microenvironment
immunotherapy
prognosis
Immunologic diseases. Allergy
RC581-607
Yongdong Guo
Ronglin Wang
Junqiang Li
Yang Song
Jie Min
Ting Zhao
Lei Hua
Jingjie Shi
Chao Zhang
Peixiang Ma
Cheng Yang
Liaoliao Zhu
Dongxue Gan
Shanshan Li
Xiaonan Liu
Haichuan Su
Comprehensive Analysis of m6A RNA Methylation Regulators and the Immune Microenvironment to Aid Immunotherapy in Pancreatic Cancer
description Pancreatic cancer (PAAD) is one of the most malignant cancers and immune microenvironment has been proved to be involved in pathogenesis of PAAD. m6A modification, related to the expression of m6A regulators, participates in the development of multiple cancers. However, the correlation between m6A regulators and immune microenvironment was largely unknown in PAAD. And because of the small sample size of pancreatic cancer in the TCGA database, it is not enough to draw a convincing conclusion. In the present study, we downloaded seven pancreatic cancer datasets with survival data and removed batch effects among these datasets to be used as the PAAD cohort to analyze the immune landscape of PAAD and the expression pattern of m6A regulators and divided the integrated dataset into cluster 1 and cluster 2 by consensus clustering for m6A regulators. Lower m6A regulators were found to be related to higher immune cell infiltration and a better survival. Moreover, we identified six m6A regulators and constructed the prognostic signature of m6A regulators. Patients with low-risk score had a higher response to immune checkpoint inhibitor and a longer overall survival. To figure out the underlying mechanism, we analyzed the cancer immunity cycle, most altered genes, gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) in risk subtypes. In summary, the present study proved m6A regulators modulated the PAAD immune microenvironment. And risk scores served as predictive indicator for immunotherapy and played a prognostic role for PAAD patients. Our study provided novel therapeutic targets to improve immunotherapy efficacy.
format article
author Yongdong Guo
Ronglin Wang
Junqiang Li
Yang Song
Jie Min
Ting Zhao
Lei Hua
Jingjie Shi
Chao Zhang
Peixiang Ma
Cheng Yang
Liaoliao Zhu
Dongxue Gan
Shanshan Li
Xiaonan Liu
Haichuan Su
author_facet Yongdong Guo
Ronglin Wang
Junqiang Li
Yang Song
Jie Min
Ting Zhao
Lei Hua
Jingjie Shi
Chao Zhang
Peixiang Ma
Cheng Yang
Liaoliao Zhu
Dongxue Gan
Shanshan Li
Xiaonan Liu
Haichuan Su
author_sort Yongdong Guo
title Comprehensive Analysis of m6A RNA Methylation Regulators and the Immune Microenvironment to Aid Immunotherapy in Pancreatic Cancer
title_short Comprehensive Analysis of m6A RNA Methylation Regulators and the Immune Microenvironment to Aid Immunotherapy in Pancreatic Cancer
title_full Comprehensive Analysis of m6A RNA Methylation Regulators and the Immune Microenvironment to Aid Immunotherapy in Pancreatic Cancer
title_fullStr Comprehensive Analysis of m6A RNA Methylation Regulators and the Immune Microenvironment to Aid Immunotherapy in Pancreatic Cancer
title_full_unstemmed Comprehensive Analysis of m6A RNA Methylation Regulators and the Immune Microenvironment to Aid Immunotherapy in Pancreatic Cancer
title_sort comprehensive analysis of m6a rna methylation regulators and the immune microenvironment to aid immunotherapy in pancreatic cancer
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/641549c322a343b08db58d183c9c6476
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