Identification of aneuploidy-related gene signature to predict survival in head and neck squamous cell carcinomas

作者全名："Liu, Yu; Yuan, Yonghua; Chen, Tao; Xiao, Hongyi; Zhang, Xiangyu; Zhang, Fujun"

作者地址："[Liu, Yu; Chen, Tao] Chongqing Med Univ, Affiliated Hosp 1, Dept Pharm, Chongqing 400016, Peoples R China; [Yuan, Yonghua] Chongqing Med Univ, Coll Pharm, Res Ctr Pharmacodynam Evaluat Engn Technol Chongqi, Chongqing 400016, Peoples R China; [Xiao, Hongyi; Zhang, Xiangyu; Zhang, Fujun] Chongqing Med Univ, Affiliated Hosp 1, Dept Oral & Maxillofacial Surg, Chongqing 400016, Peoples R China"

通信作者："Zhang, FJ (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Oral & Maxillofacial Surg, Chongqing 400016, Peoples R China."

来源：AGING-US

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001117592100028

JCR分区：Q2

影响因子：5.2

年份：2023

卷号：15

期号：22

开始页：13100

结束页：13117

文献类型：Article

关键词：head and neck squamous cell carcinomas; aneuploidy; ARS model; nomogram; therapy evaluation

摘要："Background: To parse the characteristics of aneuploidy related riskscore (ARS) model in head and neck squamous cell carcinomas (HNSC) and their predictive ability on patient prognosis.Methods: Molecular subtyping of HNSC specimens was clustered by Copy Number Variation (CNV) data from The Cancer Genome Atlas (TCGA) dataset applying consistent clustering, followed by immune condition evaluation, differentially expressed genes (DEGs) analysis and DEGs function annotation. Weighted gene co expression network analysis (WGCNA), protein-protein interaction, Univariate Cox regression analysis, least absolute shrinkage and selection operator (LASSO) and stepwise multivariate Cox regression analysis were implemented to construct an ARS model. A nomogram for clinic practice was designed by rms package. Immunotherapy evaluation and drug sensitivity prediction were also carried out.Results: We stratified HNSC patients into three different molecular subgroups, with the best prognosis in C1 cluster among 3 clusters. C1 cluster displayed greatest immune infiltration status. The most DEGs between C1 and C2 groups, mainly enriched in cell cycle and immune function. We constructed a nine-gene ARS model (ICOS, IL21R, CCR7, SELL, CYTIP, ZAP70, CCR4, S1PR4 and CD79A) that effectively differentiates between high and low-risk patients. Patients in low ARS group showed a higher sensitivity to immunotherapy. A nomogram built by integrating ARS and clinic-pathological characteristics helped predict clinic survival benefit. Drug sensitivity evaluation found that 4/9 inhibitor drugs (MK-8776, AZD5438, PD-0332991, PHA-665752) acted on the cell cycle. Conclusions: We classified 3 molecular subtypes for HNSC patients and established an ARS prognostic model, which offered a prospective direction for prognosis in HNSC."

基金机构：University [W0014]; General Project of Technology Innovation and Application Development of Chongqing Science and Technology Bureau [cstc2019jscx-msxmx 0154]

基金资助正文："This study is supported by Program for Youth Innovation in Future Medical, Chongqing MedicalUniversity (W0014) and General Project of Technology Innovation and Application Development of Chongqing Science and Technology Bureau (cstc2019jscx-msxmx 0154) .r University (W0014) and General Project of Technology Innovation and Application Development of Chongqing Science and Technology Bureau (cstc2019jscx-msxmx 0154) ."