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Identify and validate circadian regulators as potential prognostic markers and immune infiltrates in head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneity pathological malignant cancer with leading causes of morbidity and mortality. EGFR inhibitors, immune checkpoint inhibitors have become novel treatments. However, the mechanism still remained uncertain. Several studies have confirmed t...

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Autores principales: Jin, Yi, Wang, Zhanwang, Huang, Siwei, Liu, Chang, Wu, Xiangwei, Wang, Hui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10651996/
https://www.ncbi.nlm.nih.gov/pubmed/37968308
http://dx.doi.org/10.1038/s41598-023-46560-8
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author Jin, Yi
Wang, Zhanwang
Huang, Siwei
Liu, Chang
Wu, Xiangwei
Wang, Hui
author_facet Jin, Yi
Wang, Zhanwang
Huang, Siwei
Liu, Chang
Wu, Xiangwei
Wang, Hui
author_sort Jin, Yi
collection PubMed
description Head and neck squamous cell carcinoma (HNSCC) is a heterogeneity pathological malignant cancer with leading causes of morbidity and mortality. EGFR inhibitors, immune checkpoint inhibitors have become novel treatments. However, the mechanism still remained uncertain. Several studies have confirmed that the circadian rhythms induce multiple malignancies developing. We utilized multi-omics analysis to demonstrate the crosstalk between circadian clock genes and tumor microenvironment in HNSCC. Firstly, we performed the LASSO Cox regression analysis based on the 16 important clock genes. A 7-gene risk model was successfully established in TCGA and validated in GEO datasets. Next, CIBERSORT and ESTIMATE methods were performed to display the immune landscape of high risk and low risk groups, and the results showed that high abundance of mast cells activated, dendritic cells activated and neutrophils were positively correlated with poor OS. To further identify hub genes, Kaplan Meier plot was applied in all TCGA and GEO datasets and two hub genes (PER2, and PER3) were identified, especially PER3, which was found strongly associated with immune score, PDCD1, CD4 + and CD8 + T cells in HNSCCC. Moreover, to explore the innate mechanism of circadian-induced pathway, we constructed a circadian-related ceRNA regulatory network containing 34 lncRNAs, 3 miRNAs and 4 core circadian genes. In-vitro experiments also verified that Per2 or Per3 could suppressed the proliferation, migration and invasion of HNSC. This study unraveled the association between PER3 and prognosis in patients with HNSC and the innate mechanism remains to be elucidated.
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spelling pubmed-106519962023-11-15 Identify and validate circadian regulators as potential prognostic markers and immune infiltrates in head and neck squamous cell carcinoma Jin, Yi Wang, Zhanwang Huang, Siwei Liu, Chang Wu, Xiangwei Wang, Hui Sci Rep Article Head and neck squamous cell carcinoma (HNSCC) is a heterogeneity pathological malignant cancer with leading causes of morbidity and mortality. EGFR inhibitors, immune checkpoint inhibitors have become novel treatments. However, the mechanism still remained uncertain. Several studies have confirmed that the circadian rhythms induce multiple malignancies developing. We utilized multi-omics analysis to demonstrate the crosstalk between circadian clock genes and tumor microenvironment in HNSCC. Firstly, we performed the LASSO Cox regression analysis based on the 16 important clock genes. A 7-gene risk model was successfully established in TCGA and validated in GEO datasets. Next, CIBERSORT and ESTIMATE methods were performed to display the immune landscape of high risk and low risk groups, and the results showed that high abundance of mast cells activated, dendritic cells activated and neutrophils were positively correlated with poor OS. To further identify hub genes, Kaplan Meier plot was applied in all TCGA and GEO datasets and two hub genes (PER2, and PER3) were identified, especially PER3, which was found strongly associated with immune score, PDCD1, CD4 + and CD8 + T cells in HNSCCC. Moreover, to explore the innate mechanism of circadian-induced pathway, we constructed a circadian-related ceRNA regulatory network containing 34 lncRNAs, 3 miRNAs and 4 core circadian genes. In-vitro experiments also verified that Per2 or Per3 could suppressed the proliferation, migration and invasion of HNSC. This study unraveled the association between PER3 and prognosis in patients with HNSC and the innate mechanism remains to be elucidated. Nature Publishing Group UK 2023-11-15 /pmc/articles/PMC10651996/ /pubmed/37968308 http://dx.doi.org/10.1038/s41598-023-46560-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Jin, Yi
Wang, Zhanwang
Huang, Siwei
Liu, Chang
Wu, Xiangwei
Wang, Hui
Identify and validate circadian regulators as potential prognostic markers and immune infiltrates in head and neck squamous cell carcinoma
title Identify and validate circadian regulators as potential prognostic markers and immune infiltrates in head and neck squamous cell carcinoma
title_full Identify and validate circadian regulators as potential prognostic markers and immune infiltrates in head and neck squamous cell carcinoma
title_fullStr Identify and validate circadian regulators as potential prognostic markers and immune infiltrates in head and neck squamous cell carcinoma
title_full_unstemmed Identify and validate circadian regulators as potential prognostic markers and immune infiltrates in head and neck squamous cell carcinoma
title_short Identify and validate circadian regulators as potential prognostic markers and immune infiltrates in head and neck squamous cell carcinoma
title_sort identify and validate circadian regulators as potential prognostic markers and immune infiltrates in head and neck squamous cell carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10651996/
https://www.ncbi.nlm.nih.gov/pubmed/37968308
http://dx.doi.org/10.1038/s41598-023-46560-8
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