Proteogenomic insights into the biology and treatment of HPV-negative head and neck squamous cell carcinoma.
Proteogenomic insights into the biology and treatment of HPV-negative head and neck squamous cell carcinoma.
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DOI：
10.1016/j.ccell.2020.12.007
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发表时间：
2021-03-08
期刊：
影响因子：
50.3
通讯作者：
Clinical Proteomic Tumor Analysis Consortium
中科院分区：
文献类型：
--
作者：
Huang C;Chen L;Savage SR;Eguez RV;Dou Y;Li Y;da Veiga Leprevost F;Jaehnig EJ;Lei JT;Wen B;Schnaubelt M;Krug K;Song X;Cieślik M;Chang HY;Wyczalkowski MA;Li K;Colaprico A;Li QK;Clark DJ;Hu Y;Cao L;Pan J;Wang Y;Cho KC;Shi Z;Liao Y;Jiang W;Anurag M;Ji J;Yoo S;Zhou DC;Liang WW;Wendl M;Vats P;Carr SA;Mani DR;Zhang Z;Qian J;Chen XS;Pico AR;Wang P;Chinnaiyan AM;Ketchum KA;Kinsinger CR;Robles AI;An E;Hiltke T;Mesri M;Thiagarajan M;Weaver AM;Sikora AG;Lubiński J;Wierzbicka M;Wiznerowicz M;Satpathy S;Gillette MA;Miles G;Ellis MJ;Omenn GS;Rodriguez H;Boja ES;Dhanasekaran SM;Ding L;Nesvizhskii AI;El-Naggar AK;Chan DW;Zhang H;Zhang B;Clinical Proteomic Tumor Analysis Consortium
我们对108例人乳头状瘤病毒（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相关蛋白和磷酸化位点进行分类，优先考虑拷贝数驱动因素，并突出RNA加工基因的致癌作用。FAT 1截短突变和11q13.3扩增之间的互斥性的蛋白质组学研究揭示了作为一种常见的功能后果的肌动蛋白动力学失调。磷酸化蛋白质组学表征了EGFR激活的两种模式，提出了基于EGFR配体丰度对HNSCC进行分层的新策略，用于抑制性EGFR单克隆抗体的有效治疗。免疫调节基因的广泛缺失解释了免疫冷肿瘤中的低免疫浸润，而多种免疫检查点蛋白的一致上调可能是免疫热肿瘤中抗PD-1单药治疗耐药性的基础。多组学分析确定了三种分子亚型，分别具有用CDK抑制剂、抗EGFR抗体疗法和免疫疗法治疗的高潜力。总而言之，蛋白基因组学提供了一个系统的框架，告知HNSCC生物学和治疗。Huang等人报告了对108例HPV阴性头颈部鳞状细胞癌（HNSCC）的蛋白基因组学研究。除了为致病性见解创造全面的资源外，多组学分析还确定了可能为更精确的治疗方法提供信息的治疗假设。
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-PD-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. Huang et al. report a proteogenomic study on 108 HPV-negative head and neck squamous cell carcinomas (HNSCCs). In addition to creating a comprehensive resource for pathogenic insights, multi-omic analysis identifies therapeutic hypotheses that may inform more precise approaches to treatment.
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影响因子：
14.9
作者：
Babiceanu M;Qin F;Xie Z;Jia Y;Lopez K;Janus N;Facemire L;Kumar S;Pang Y;Qi Y;Lazar IM;Li H
通讯作者：
Li H
影响因子：
14.9
作者：
Almeida LG;Sakabe NJ;deOliveira AR;Silva MC;Mundstein AS;Cohen T;Chen YT;Chua R;Gurung S;Gnjatic S;Jungbluth AA;Caballero OL;Bairoch A;Kiesler E;White SL;Simpson AJ;Old LJ;Camargo AA;Vasconcelos AT
通讯作者：
Vasconcelos AT
DOI：
10.4161/15384101.2014.977067
发表时间：
2015
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Benada J;Burdová K;Lidak T;von Morgen P;Macurek L
通讯作者：
Macurek L
影响因子：
45.3
作者：
Baselga, J;Trigo, JM;Eckardt, A
通讯作者：
Eckardt, A
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y