当前位置: X-MOL 学术Cancer Cell › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Proteogenomic insights into the biology and treatment of HPV-negative head and neck squamous cell carcinoma
Cancer Cell ( IF 48.8 ) Pub Date : 2021-01-07 , DOI: 10.1016/j.ccell.2020.12.007
Chen Huang 1 , Lijun Chen 2 , Sara R Savage 1 , Rodrigo Vargas Eguez 2 , Yongchao Dou 1 , Yize Li 3 , Felipe da Veiga Leprevost 4 , Eric J Jaehnig 1 , Jonathan T Lei 1 , Bo Wen 1 , Michael Schnaubelt 2 , Karsten Krug 5 , Xiaoyu Song 6 , Marcin Cieślik 7 , Hui-Yin Chang 4 , Matthew A Wyczalkowski 3 , Kai Li 1 , Antonio Colaprico 8 , Qing Kay Li 2 , David J Clark 2 , Yingwei Hu 2 , Liwei Cao 2 , Jianbo Pan 9 , Yuefan Wang 2 , Kyung-Cho Cho 2 , Zhiao Shi 1 , Yuxing Liao 1 , Wen Jiang 1 , Meenakshi Anurag 10 , Jiayi Ji 6 , Seungyeul Yoo 11 , Daniel Cui Zhou 3 , Wen-Wei Liang 3 , Michael Wendl 3 , Pankaj Vats 12 , Steven A Carr 5 , D R Mani 5 , Zhen Zhang 2 , Jiang Qian 13 , Xi S Chen 8 , Alexander R Pico 14 , Pei Wang 11 , Arul M Chinnaiyan 7 , Karen A Ketchum 15 , Christopher R Kinsinger 16 , Ana I Robles 16 , Eunkyung An 16 , Tara Hiltke 16 , Mehdi Mesri 16 , Mathangi Thiagarajan 17 , Alissa M Weaver 18 , Andrew G Sikora 19 , Jan Lubiński 20 , Małgorzata Wierzbicka 21 , Maciej Wiznerowicz 22 , Shankha Satpathy 5 , Michael A Gillette 23 , George Miles 1 , Matthew J Ellis 10 , Gilbert S Omenn 24 , Henry Rodriguez 16 , Emily S Boja 16 , Saravana M Dhanasekaran 25 , Li Ding 3 , Alexey I Nesvizhskii 7 , Adel K El-Naggar 26 , Daniel W Chan 2 , Hui Zhang 2 , Bing Zhang 1 ,
Affiliation  

We present a proteogenomic study of 108 human papilloma virus (HPV)-negative head and neck squamous cell carcinomas (HNSCCs). Proteomic analysis systematically catalogs HNSCC-associated proteins and phosphosites, prioritizes copy number drivers, and highlights an oncogenic role for RNA processing genes. Proteomic investigation of mutual exclusivity between FAT1 truncating mutations and 11q13.3 amplifications reveals dysregulated actin dynamics as a common functional consequence. Phosphoproteomics characterizes two modes of EGFR activation, suggesting a new strategy to stratify HNSCCs based on EGFR ligand abundance for effective treatment with inhibitory EGFR monoclonal antibodies. Widespread deletion of immune modulatory genes accounts for low immune infiltration in immune-cold tumors, whereas concordant upregulation of multiple immune checkpoint proteins may underlie resistance to anti-programmed cell death protein 1 monotherapy in immune-hot tumors. Multi-omic analysis identifies three molecular subtypes with high potential for treatment with CDK inhibitors, anti-EGFR antibody therapy, and immunotherapy, respectively. Altogether, proteogenomics provides a systematic framework to inform HNSCC biology and treatment.



中文翻译:

蛋白质组学对 HPV 阴性头颈部鳞状细胞癌生物学和治疗的见解

我们对 108 例人乳头瘤病毒 (HPV) 阴性的头颈部鳞状细胞癌 (HNSCC) 进行了蛋白质组学研究。蛋白质组学分析系统地对 HNSCC 相关蛋白和磷酸位点进行分类,优先考虑拷贝数驱动因素,并突出 RNA 加工基因的致癌作用。FAT1互斥性的蛋白质组学研究截断突变和 11q13.3 扩增揭示了肌动蛋白动力学失调是一种常见的功能后果。磷酸蛋白质组学表征了 EGFR 激活的两种模式,提出了一种基于 EGFR 配体丰度对 HNSCC 进行分层的新策略,以有效治疗抑制性 EGFR 单克隆抗体。免疫调节基因的广泛缺失是免疫冷肿瘤免疫浸润低的原因,而多个免疫检查点蛋白的一致上调可能是免疫热肿瘤对抗程序性细胞死亡蛋白 1 单一疗法耐药的基础。多组学分析确定了三种具有高潜力的分子亚型,分别用于 CDK 抑制剂、抗 EGFR 抗体治疗和免疫治疗。共,

更新日期:2021-03-08
down
wechat
bug