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Circadian Regulator-Mediated Molecular Subtypes Depict the Features of Tumor Microenvironment and Indicate Prognosis in Head and Neck Squamous Cell Carcinoma

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机构： [1]Department of Otolaryngology, Shanghai Eye & ENT Hospital, Fudan University, Shanghai 200031, China. [2]Five-Year Program Clinical Medicine, Grade of 2019, West China School of Medicine, Sichuan University, Chengdu, 610041 Sichuan, China. [3]Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Fudan University, Shanghai 200032, China. [4]Department of Gastroenterology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China. [5]Department of Otolaryngology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China. [6]Laboratory of Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China. [7]Key Laboratory of Birth Defects, Children's Hospital of Fudan University, Shanghai 201102, China.

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Circadian rhythm is involved in multiple biological activities and implicated in cancer development. However, the role of circadian rhythm in head and neck squamous cell carcinoma (HNSCC) has not been fully interpreted yet. Herein, the present study set out to explore the significance of circadian regulator genes (CRGs) in HNSCC.The molecular landscape and clinical significance of 13 CRGs in HNSCC were explored based on The Cancer Genome Atlas (TCGA). The biological functions of PER3, a key CRG, were validated by cellular experiments. The correlation of CRGs with microenvironment, pathway activities, and prognosis was determined by bioinformatic algorithms. A novel circadian score was introduced to evaluate the circadian modification pattern of each patient and further validated in an independent cohort from the Gene Expression Omnibus (GEO) dataset.CRGs presented high heterogeneity in HNSCC at both genomic and transcriptomic levels. Specifically, PER3 indicated a better prognosis and inhibited HNSCC cell proliferation. Moreover, HNSCC tissues displayed three circadian regulator patterns with distinct clinical outcomes, transcriptomic characteristics, and microenvironment features. Circadian score was an independent risk factor and exhibited excellent predictive efficiency in both the training cohort from the TCGA database and the validation cohort from the GEO database.CRGs played an indispensable role in HNSCC development. An in-depth exploration of circadian rhythm would improve the understanding of HNSCC carcinogenesis and confer novel insights for future clinical practices.Copyright © 2023 Ling Aye et al.

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出版当年[2023]版：

大类 | 3 区医学

小类 | 4 区免疫学

最新[2023]版：

大类 | 3 区医学

小类 | 4 区免疫学

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第一作者机构： [1]Department of Otolaryngology, Shanghai Eye & ENT Hospital, Fudan University, Shanghai 200031, China.

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通讯机构： [6]Laboratory of Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China. [7]Key Laboratory of Birth Defects, Children's Hospital of Fudan University, Shanghai 201102, China.

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