m6A Regulator-Associated Modification Patterns and Immune Infiltration of the Tumor Microenvironment in Hepatocarcinoma
Background: Immunotherapy elicits durable responses in many tumors. Nevertheless, the positive response to immunotherapy always depends on the dynamic interactions between the tumor cells and infiltrating lymphocytes in the tumor microenvironment (TME). Currently, the application of immunotherapy in...
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Frontiers Media S.A.
2021-07-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.687756/full |
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doaj-23b826c5a7fe4e08a81ba4c2de8a76d4 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jianhao Li Jianhao Li Weiwei Wang Yubing Zhou Yubing Zhou Liwen Liu Liwen Liu Guizhen Zhang Guizhen Zhang Kelei Guan Xichun Cui Xin Liu Xin Liu Maoxin Huang Guangying Cui Guangying Cui Ranran Sun Ranran Sun |
spellingShingle |
Jianhao Li Jianhao Li Weiwei Wang Yubing Zhou Yubing Zhou Liwen Liu Liwen Liu Guizhen Zhang Guizhen Zhang Kelei Guan Xichun Cui Xin Liu Xin Liu Maoxin Huang Guangying Cui Guangying Cui Ranran Sun Ranran Sun m6A Regulator-Associated Modification Patterns and Immune Infiltration of the Tumor Microenvironment in Hepatocarcinoma Frontiers in Cell and Developmental Biology N6-methyladenosine hepatocellular carcinoma tumor microenvironment prognosis immune infiltration |
author_facet |
Jianhao Li Jianhao Li Weiwei Wang Yubing Zhou Yubing Zhou Liwen Liu Liwen Liu Guizhen Zhang Guizhen Zhang Kelei Guan Xichun Cui Xin Liu Xin Liu Maoxin Huang Guangying Cui Guangying Cui Ranran Sun Ranran Sun |
author_sort |
Jianhao Li |
title |
m6A Regulator-Associated Modification Patterns and Immune Infiltration of the Tumor Microenvironment in Hepatocarcinoma |
title_short |
m6A Regulator-Associated Modification Patterns and Immune Infiltration of the Tumor Microenvironment in Hepatocarcinoma |
title_full |
m6A Regulator-Associated Modification Patterns and Immune Infiltration of the Tumor Microenvironment in Hepatocarcinoma |
title_fullStr |
m6A Regulator-Associated Modification Patterns and Immune Infiltration of the Tumor Microenvironment in Hepatocarcinoma |
title_full_unstemmed |
m6A Regulator-Associated Modification Patterns and Immune Infiltration of the Tumor Microenvironment in Hepatocarcinoma |
title_sort |
m6a regulator-associated modification patterns and immune infiltration of the tumor microenvironment in hepatocarcinoma |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cell and Developmental Biology |
issn |
2296-634X |
publishDate |
2021-07-01 |
description |
Background: Immunotherapy elicits durable responses in many tumors. Nevertheless, the positive response to immunotherapy always depends on the dynamic interactions between the tumor cells and infiltrating lymphocytes in the tumor microenvironment (TME). Currently, the application of immunotherapy in hepatocellular carcinoma (HCC) has achieved limited success. The ectopic modification of N6-methyladenosine (m6A) is a common feature in multiple tumors. However, the relationship between m6A modification with HCC clinical features, prognosis, immune cell infiltration, and immunotherapy efficacy remains unclear.Materials and Methods: Here, we comprehensively evaluated m6A modification clusters based on 22 m6A regulators and systematically explored the relationship between m6A modification with tumor progression, prognosis, and immune cell infiltration characteristics. The m6Ascore was calculated by principal component analysis to quantify the m6A modifications of individual patients. Key regulators involved in immunoregulation in HCC were identified using immunohistochemistry and immunofluorescence.Results: Three distinct m6A modification clusters were identified. The m6A clusters were significantly associated with clinical features, prognosis, and immune cell infiltration. The three clusters were highly consistent with the three tumor immune phenotypes, i.e., immune-excluded, immune-inflamed, and immune-desert. Comprehensive bioinformatics analysis revealed that high m6Ascore was closely associated with tumor progression, poor prognosis, and immunotherapy non-response. m6A regulators were dysregulated in HCC tissues. Hence, they play a role as predictors of poor prognosis. Tissue microarray demonstrated that overexpressed YTHDF1 was associated with low CD3+ and CD8+ T cell infiltration in HCC.Conclusion: Our findings demonstrate that m6A modification patterns play a crucial role in the tumor immune microenvironment and the prognosis of HCC. High YTHDF1 expression is closely associated with low CD3+ and CD8+ T cell infiltration in HCC. |
topic |
N6-methyladenosine hepatocellular carcinoma tumor microenvironment prognosis immune infiltration |
url |
https://www.frontiersin.org/articles/10.3389/fcell.2021.687756/full |
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doaj-23b826c5a7fe4e08a81ba4c2de8a76d42021-07-02T05:11:53ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-07-01910.3389/fcell.2021.687756687756m6A Regulator-Associated Modification Patterns and Immune Infiltration of the Tumor Microenvironment in HepatocarcinomaJianhao Li0Jianhao Li1Weiwei Wang2Yubing Zhou3Yubing Zhou4Liwen Liu5Liwen Liu6Guizhen Zhang7Guizhen Zhang8Kelei Guan9Xichun Cui10Xin Liu11Xin Liu12Maoxin Huang13Guangying Cui14Guangying Cui15Ranran Sun16Ranran Sun17Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaKey Laboratory of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaKey Laboratory of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaPrecision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaKey Laboratory of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaPrecision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaKey Laboratory of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaKey Laboratory of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaPrecision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaKey Laboratory of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Dermatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaPrecision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaKey Laboratory of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaPrecision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaKey Laboratory of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaBackground: Immunotherapy elicits durable responses in many tumors. Nevertheless, the positive response to immunotherapy always depends on the dynamic interactions between the tumor cells and infiltrating lymphocytes in the tumor microenvironment (TME). Currently, the application of immunotherapy in hepatocellular carcinoma (HCC) has achieved limited success. The ectopic modification of N6-methyladenosine (m6A) is a common feature in multiple tumors. However, the relationship between m6A modification with HCC clinical features, prognosis, immune cell infiltration, and immunotherapy efficacy remains unclear.Materials and Methods: Here, we comprehensively evaluated m6A modification clusters based on 22 m6A regulators and systematically explored the relationship between m6A modification with tumor progression, prognosis, and immune cell infiltration characteristics. The m6Ascore was calculated by principal component analysis to quantify the m6A modifications of individual patients. Key regulators involved in immunoregulation in HCC were identified using immunohistochemistry and immunofluorescence.Results: Three distinct m6A modification clusters were identified. The m6A clusters were significantly associated with clinical features, prognosis, and immune cell infiltration. The three clusters were highly consistent with the three tumor immune phenotypes, i.e., immune-excluded, immune-inflamed, and immune-desert. Comprehensive bioinformatics analysis revealed that high m6Ascore was closely associated with tumor progression, poor prognosis, and immunotherapy non-response. m6A regulators were dysregulated in HCC tissues. Hence, they play a role as predictors of poor prognosis. Tissue microarray demonstrated that overexpressed YTHDF1 was associated with low CD3+ and CD8+ T cell infiltration in HCC.Conclusion: Our findings demonstrate that m6A modification patterns play a crucial role in the tumor immune microenvironment and the prognosis of HCC. High YTHDF1 expression is closely associated with low CD3+ and CD8+ T cell infiltration in HCC.https://www.frontiersin.org/articles/10.3389/fcell.2021.687756/fullN6-methyladenosinehepatocellular carcinomatumor microenvironmentprognosisimmune infiltration |