DNA Methylation Regulator-Meditated Modification Patterns Define the Distinct Tumor Microenvironment in Lung Adenocarcinoma

BackgroundEpigenetic changes of lung adenocarcinoma (LUAD) have been reported to be a relevant factor in tumorigenesis and cancer progression. However, the molecular mechanisms responsible for DNA methylation patterns in the tumor immune-infiltrating microenvironment and in cancer immunotherapy rema...

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Main Authors: Didi Yuan, Zehong Wei, Yicheng Wang, Fang Cheng, Yujie Zeng, Li Yang, Shangyu Zhang, Jianbo Li, Renkuan Tang
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-09-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2021.734873/full
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spelling doaj-1710701861764898976a0ae10ac8a15b2021-09-06T05:54:59ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-09-011110.3389/fonc.2021.734873734873DNA Methylation Regulator-Meditated Modification Patterns Define the Distinct Tumor Microenvironment in Lung AdenocarcinomaDidi YuanZehong WeiYicheng WangFang ChengYujie ZengLi YangShangyu ZhangJianbo LiRenkuan TangBackgroundEpigenetic changes of lung adenocarcinoma (LUAD) have been reported to be a relevant factor in tumorigenesis and cancer progression. However, the molecular mechanisms responsible for DNA methylation patterns in the tumor immune-infiltrating microenvironment and in cancer immunotherapy remain unclear.MethodsWe conducted a global analysis of the DNA methylation modification pattern (DMP) and immune cell-infiltrating characteristics of LUAD patients based on 21 DNA methylation regulators. A DNA methylation score (DMS) system was constructed to quantify the DMP model in each patient and estimate their potential benefit from immunotherapy.ResultsTwo DNA methylation modification patterns able to distinctly characterize the immune microenvironment characterization were identified among 513 LUAD samples. A lower DMS, characterized by increased CTLA-4/PD-1/L1 gene expression, greater methylation modifications, and tumor mutation burden, characterized a noninflamed phenotype with worse survival. A higher DMS, characterized by decreased methylation modification, a greater stromal-relevant response, and immune hyperactivation, characterized an inflamed phenotype with better prognosis. Moreover, a lower DMS indicated an increased mutation load and exhibited a poor immunotherapeutic response in the anti-CTLA-4/PD-1/PD-L1 cohort.ConclusionEvaluating the DNA methylation modification pattern of LUAD patients could enhance our understanding of the features of tumor microenvironment characterization and may promote more favorable immunotherapy strategies.https://www.frontiersin.org/articles/10.3389/fonc.2021.734873/fulllung adenocarcinoma (LUAD)DNA methylationtumor microenvironmentimmunotherapymutation burden
collection DOAJ
language English
format Article
sources DOAJ
author Didi Yuan
Zehong Wei
Yicheng Wang
Fang Cheng
Yujie Zeng
Li Yang
Shangyu Zhang
Jianbo Li
Renkuan Tang
spellingShingle Didi Yuan
Zehong Wei
Yicheng Wang
Fang Cheng
Yujie Zeng
Li Yang
Shangyu Zhang
Jianbo Li
Renkuan Tang
DNA Methylation Regulator-Meditated Modification Patterns Define the Distinct Tumor Microenvironment in Lung Adenocarcinoma
Frontiers in Oncology
lung adenocarcinoma (LUAD)
DNA methylation
tumor microenvironment
immunotherapy
mutation burden
author_facet Didi Yuan
Zehong Wei
Yicheng Wang
Fang Cheng
Yujie Zeng
Li Yang
Shangyu Zhang
Jianbo Li
Renkuan Tang
author_sort Didi Yuan
title DNA Methylation Regulator-Meditated Modification Patterns Define the Distinct Tumor Microenvironment in Lung Adenocarcinoma
title_short DNA Methylation Regulator-Meditated Modification Patterns Define the Distinct Tumor Microenvironment in Lung Adenocarcinoma
title_full DNA Methylation Regulator-Meditated Modification Patterns Define the Distinct Tumor Microenvironment in Lung Adenocarcinoma
title_fullStr DNA Methylation Regulator-Meditated Modification Patterns Define the Distinct Tumor Microenvironment in Lung Adenocarcinoma
title_full_unstemmed DNA Methylation Regulator-Meditated Modification Patterns Define the Distinct Tumor Microenvironment in Lung Adenocarcinoma
title_sort dna methylation regulator-meditated modification patterns define the distinct tumor microenvironment in lung adenocarcinoma
publisher Frontiers Media S.A.
series Frontiers in Oncology
issn 2234-943X
publishDate 2021-09-01
description BackgroundEpigenetic changes of lung adenocarcinoma (LUAD) have been reported to be a relevant factor in tumorigenesis and cancer progression. However, the molecular mechanisms responsible for DNA methylation patterns in the tumor immune-infiltrating microenvironment and in cancer immunotherapy remain unclear.MethodsWe conducted a global analysis of the DNA methylation modification pattern (DMP) and immune cell-infiltrating characteristics of LUAD patients based on 21 DNA methylation regulators. A DNA methylation score (DMS) system was constructed to quantify the DMP model in each patient and estimate their potential benefit from immunotherapy.ResultsTwo DNA methylation modification patterns able to distinctly characterize the immune microenvironment characterization were identified among 513 LUAD samples. A lower DMS, characterized by increased CTLA-4/PD-1/L1 gene expression, greater methylation modifications, and tumor mutation burden, characterized a noninflamed phenotype with worse survival. A higher DMS, characterized by decreased methylation modification, a greater stromal-relevant response, and immune hyperactivation, characterized an inflamed phenotype with better prognosis. Moreover, a lower DMS indicated an increased mutation load and exhibited a poor immunotherapeutic response in the anti-CTLA-4/PD-1/PD-L1 cohort.ConclusionEvaluating the DNA methylation modification pattern of LUAD patients could enhance our understanding of the features of tumor microenvironment characterization and may promote more favorable immunotherapy strategies.
topic lung adenocarcinoma (LUAD)
DNA methylation
tumor microenvironment
immunotherapy
mutation burden
url https://www.frontiersin.org/articles/10.3389/fonc.2021.734873/full
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