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pmid:32622331

Comprehensive Analysis of the PD-L1 and Immune Infiltrates of m6A RNA Methylation Regulators in Head and Neck Squamous Cell Carcinoma.

Lilan Yi · Guowu Wu · Longhua Guo · Xiaofang Zou · Ping Huang

Molecular therapy. Nucleic acids · 2020 doi:10.1016/j.omtn.2020.06.001

Paper

complete

Experiment

partial

Data

partial

Analysis

partial

Execution

absent

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title
Comprehensive Analysis of the PD-L1 and Immune Infiltrates of m6A RNA Methylation Regulators in Head and Neck Squamous Cell Carcinoma.
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10.1016/j.omtn.2020.06.001
pmid
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Lilan Yi
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Guowu Wu
[2]
Longhua Guo
[3]
Xiaofang Zou
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Ping Huang
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Molecular therapy. Nucleic acids
year
2020
abstract
Because most studies have focused on the intrinsic carcinogenic pathways of tumors, the underlying role of N6-methyladenosine (m6A) methylation in tumor immune microenvironment (TIME) remains elusive. Herein, we systematically explored the correlations of prominent m6A regulators with PD-L1 and immune infiltrates in 769 head and neck squamous cell carcinomas (HNSCCs; The Cancer Genome Atlas [TCGA] cohort, n = 499; GSE65858 cohort, n = 270). The PD-L1 expression evidently associated with m6A regulators. Two molecular subtypes (cluster1/2) were identified by consensus clustering for 15 m6A regulators. The cluster2 preferentially associated with favorable prognosis, upregulated PD-L1 expression, higher immunoscore, and distinct immune cell infiltration. The hallmarks of G2M checkpoint, mTORC1 signaling, and PI3K/AKT/mTOR signaling were remarkably enriched in the cluster1. A prognostic risk score was constructed using seven m6A regulator-associated signatures that represented an independent prognosis factor for HNSCC. Patients with low-risk score exhibited higher immunoscore and upregulated PD-L1 expression than patients with high-risk score. Consistently, m6A regulators showed the same influence on immune modulation and survival in external GSE65858 cohort. Further analysis revealed that m6A regulator-based signatures were implicated in TIME and their copy-number alterations dynamically affected the abundance of tumor-infiltrating immune cells. Collectively, our study elucidated the important role of m6A methylation in TIME of HNSCC. The proposed m6A regulator-based signatures might serve as crucial mediators of TIME in HNSCC, representing promising therapeutic targets in improving immunotherapeutic efficacy.
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Herein, we systematically explored the correlations of prominent m6A regulators with PD-L1 and immune infiltrates in 769 head and neck squamous cell carcinomas (HNSCCs; The Cancer Genome Atlas [TCGA] cohort, n = 499; GSE65858 cohort, n = 270). The PD-L1 expression evidently associated with m6A regulators. Two molecular subtypes (cluster1/2) were identified by consensus clustering for 15 m6A regulators. The cluster2 preferentially associated with favorable prognosis, upregulated PD-L1 expression, higher immunoscore, and distinct immune cell infiltration. The hallmarks of G2M checkpoint, mTORC1 signaling, and PI3K/AKT/mTOR signaling were remarkably enriched in the cluster1. A prognostic risk score was constructed using seven m6A regulator-associated signatures that represented an independent prognosis factor for HNSCC. Patients with low-risk score exhibited higher immunoscore and upregulated PD-L1 expression than patients with high-risk score. 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