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Upregulated YTHDF1 associates with tumor immune microenvironment in head and neck squamous cell carcinomas

BACKGROUND: The nature of the tumor immune microenvironment (TME) is essential for the head and neck squamous cell carcinomas (HNSCC) initiation, prognosis, and response to immunotherapy. However, its gene regulatory network remains to be elucidated. METHODS: To identify N6-methyladenosine (m6A) reg...

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Autores principales: Huang, Yongsheng, Liao, Jianwei, Wu, Sangqing, Ye, Yuchu, Zeng, Haicang, Liang, Faya, Yin, Xinke, Jiang, Yuanling, Ouyang, Nengtai, Han, Ping, Huang, Xiaoming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9745380/
https://www.ncbi.nlm.nih.gov/pubmed/36523307
http://dx.doi.org/10.21037/tcr-22-503
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author Huang, Yongsheng
Liao, Jianwei
Wu, Sangqing
Ye, Yuchu
Zeng, Haicang
Liang, Faya
Yin, Xinke
Jiang, Yuanling
Ouyang, Nengtai
Han, Ping
Huang, Xiaoming
author_facet Huang, Yongsheng
Liao, Jianwei
Wu, Sangqing
Ye, Yuchu
Zeng, Haicang
Liang, Faya
Yin, Xinke
Jiang, Yuanling
Ouyang, Nengtai
Han, Ping
Huang, Xiaoming
author_sort Huang, Yongsheng
collection PubMed
description BACKGROUND: The nature of the tumor immune microenvironment (TME) is essential for the head and neck squamous cell carcinomas (HNSCC) initiation, prognosis, and response to immunotherapy. However, its gene regulatory network remains to be elucidated. METHODS: To identify N6-methyladenosine (m6A) regulators that are involved in regulating the HNSCC TME, a computational screen was applied to The Cancer Genome Atlas (TCGA) HNSCC patient samples. The effects of mutation, copy number variation (CNV), and transcriptional regulation on YTHDF1 expression were analyzed. We analyzed the TME infiltration, cancer-immunity cycle activities, and YTHDF1-related Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. RESULTS: Among the 24 m6A regulators, 3 factors (YTHDF1, ELAVL1, and METTL3) were highly correlated with TME infiltration. As the top candidate, YTHDF1 was up-regulated and amplified in HNSCC. YTHDF1 promoter gains active histone marks and high chromatin accessibility, which might be transcriptionally activated by SOX2 and TP63. Moreover, YTHDF1 expression significantly associates with tumor malignant phenotype in HNSCC, which has a positive correlation with CD4+ T cells and a negative correlation with CD8+ T cells infiltration. Specifically, YTHDF1 expression is negatively associated with the cancer-immunity cycle and immune checkpoint inhibitors. In terms of the underlying biological mechanisms, YTHDF1 may interact with YTHDF2/3 to regulate several vital immune-related pathways. CONCLUSIONS: We identify YTHDF1 associated with TME and elucidate an underlying mechanism of immune escape in HNSCC, which might be used as a predictive marker in guiding immunotherapy.
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spelling pubmed-97453802022-12-14 Upregulated YTHDF1 associates with tumor immune microenvironment in head and neck squamous cell carcinomas Huang, Yongsheng Liao, Jianwei Wu, Sangqing Ye, Yuchu Zeng, Haicang Liang, Faya Yin, Xinke Jiang, Yuanling Ouyang, Nengtai Han, Ping Huang, Xiaoming Transl Cancer Res Original Article BACKGROUND: The nature of the tumor immune microenvironment (TME) is essential for the head and neck squamous cell carcinomas (HNSCC) initiation, prognosis, and response to immunotherapy. However, its gene regulatory network remains to be elucidated. METHODS: To identify N6-methyladenosine (m6A) regulators that are involved in regulating the HNSCC TME, a computational screen was applied to The Cancer Genome Atlas (TCGA) HNSCC patient samples. The effects of mutation, copy number variation (CNV), and transcriptional regulation on YTHDF1 expression were analyzed. We analyzed the TME infiltration, cancer-immunity cycle activities, and YTHDF1-related Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. RESULTS: Among the 24 m6A regulators, 3 factors (YTHDF1, ELAVL1, and METTL3) were highly correlated with TME infiltration. As the top candidate, YTHDF1 was up-regulated and amplified in HNSCC. YTHDF1 promoter gains active histone marks and high chromatin accessibility, which might be transcriptionally activated by SOX2 and TP63. Moreover, YTHDF1 expression significantly associates with tumor malignant phenotype in HNSCC, which has a positive correlation with CD4+ T cells and a negative correlation with CD8+ T cells infiltration. Specifically, YTHDF1 expression is negatively associated with the cancer-immunity cycle and immune checkpoint inhibitors. In terms of the underlying biological mechanisms, YTHDF1 may interact with YTHDF2/3 to regulate several vital immune-related pathways. CONCLUSIONS: We identify YTHDF1 associated with TME and elucidate an underlying mechanism of immune escape in HNSCC, which might be used as a predictive marker in guiding immunotherapy. AME Publishing Company 2022-11 /pmc/articles/PMC9745380/ /pubmed/36523307 http://dx.doi.org/10.21037/tcr-22-503 Text en 2022 Translational Cancer Research. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Original Article
Huang, Yongsheng
Liao, Jianwei
Wu, Sangqing
Ye, Yuchu
Zeng, Haicang
Liang, Faya
Yin, Xinke
Jiang, Yuanling
Ouyang, Nengtai
Han, Ping
Huang, Xiaoming
Upregulated YTHDF1 associates with tumor immune microenvironment in head and neck squamous cell carcinomas
title Upregulated YTHDF1 associates with tumor immune microenvironment in head and neck squamous cell carcinomas
title_full Upregulated YTHDF1 associates with tumor immune microenvironment in head and neck squamous cell carcinomas
title_fullStr Upregulated YTHDF1 associates with tumor immune microenvironment in head and neck squamous cell carcinomas
title_full_unstemmed Upregulated YTHDF1 associates with tumor immune microenvironment in head and neck squamous cell carcinomas
title_short Upregulated YTHDF1 associates with tumor immune microenvironment in head and neck squamous cell carcinomas
title_sort upregulated ythdf1 associates with tumor immune microenvironment in head and neck squamous cell carcinomas
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9745380/
https://www.ncbi.nlm.nih.gov/pubmed/36523307
http://dx.doi.org/10.21037/tcr-22-503
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