干旱区生态环境知识资源中心(Arid): Development and Validation of a Combined Hypoxia and Immune Prognostic Classifier for Head and Neck Cancer

Arid

DOI	10.1158/1078-0432.CCR-18-3314
	Development and Validation of a Combined Hypoxia and Immune Prognostic Classifier for Head and Neck Cancer
	Brooks, Jill M.1,2; Menezes, Albert N.2; Ibrahim, Maha 2,3; Archer, Lucinda 4; Lal, Neeraj 5; Bagnall, Christopher J.6; von Zeidler, Sandra V.7; Valentine, Helen R.8; Spruce, Rachel J.1,2; Batis, Nikolaos 1,2; Bryant, Jennifer L.1,2; Hartley, Margaret 1,2; Kaul, Baksho 9; Ryan, Gordon B.1,2; Bao, Riyue 10; Khattri, Arun 10; Lee, Steven P.5; Ogbureke, Kalu U. E.11; Middleton, Gary 5; Tennant, Daniel A.9; Beggs, Andrew D.2; Deeks, Jonathan 4,12,13; West, Catharine M. L.8; Cazier, Jean-Baptiste 2; Willcox, Benjamin E.5; Seiwert, Tanguy Y.10; Mehanna, Hisham 1,2
通讯作者	Mehanna, Hisham
来源期刊	CLINICAL CANCER RESEARCH
ISSN	1078-0432
EISSN	1557-3265
出版年	2019
卷号	25 期号:17 页码:5315-5328
英文摘要	Purpose: Intratumoral hypoxia and immunity have been correlated with patient outcome in various tumor settings. However, these factors are not currently considered for treatment selection in head and neck cancer (HNC) due to lack of validated biomarkers. Here we sought to develop a hypoxiaimmune classifier with potential application in patient prognostication and prediction of response to targeted therapy. Experimental Design: A 54-gene hypoxia-immune signature was constructed on the basis of literature review. Gene expression was analyzed in silico using the The Cancer Genome Atlas (TCGA) HNC dataset (n = 275) and validated using two independent cohorts (n = 130 and 123). IHC was used to investigate the utility of a simplified protein signature. The spatial distribution of hypoxia and immune markers was examined using multiplex immunofluorescence staining. Results: Unsupervised hierarchical clustering of TCGA dataset (development cohort) identified three patient subgroups with distinct hypoxia-immune phenotypes and survival profiles: hypoxia(low)/immune(high), hypoxia(high)/immune(low), and mixed, with 5-year overall survival (OS) rates of 71%, 51%, and 49%, respectively (P = 0.0015). The prognostic relevance of the hypoxia-immune gene signature was replicated in two independent validation cohorts. Only PDL1 and intratumoral CD3 protein expression were associated with improved OS on multivariate analysis. Hypoxia(low)/immune(high) and hypoxia(high)/immune(low) tumors were over-represented in inflamed and immune-desert microenvironmental profiles, respectively. Multiplex staining demonstrated an inverse correlation between CA-IX expression and prevalence of intratumoral CD3(+) T cells (r = -0.5464; P = 0.0377), further corroborating the transcription-based classification. Conclusions: We developed and validated a hypoxiaimmune prognostic transcriptional classifier, which may have clinical application to guide the use of hypoxia modification and targeted immunotherapies for the treatment of HNC.
类型	Article
语种	英语
国家	England ; Egypt ; Brazil ; USA
开放获取类型	Green Published, Bronze
收录类别	SCI-E
WOS记录号	WOS:000484118300017
WOS关键词	SQUAMOUS-CELL CARCINOMA ; EPIDERMAL-GROWTH-FACTOR ; INFILTRATING LYMPHOCYTES PREDICT ; HUMAN-PAPILLOMAVIRUS ; PD-L1 EXPRESSION ; FACTOR RECEPTOR ; UP-REGULATION ; PHASE-III ; HPV ; RADIOTHERAPY
WOS类目	Oncology
WOS研究方向	Oncology
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/214931
作者单位	1.Univ Birmingham, Inst Head & Neck Studies & Educ, Birmingham, W Midlands, England; 2.Univ Birmingham, Inst Canc & Genom Sci, Birmingham, W Midlands, England; 3.Assiut Univ, South Egypt Canc Inst, Assiut, Egypt; 4.Univ Birmingham, Inst Appl Hlth Res, Birmingham, W Midlands, England; 5.Univ Birmingham, Inst Immunol & Immunotherapy, Birmingham, W Midlands, England; 6.Univ Birmingham, Human Biomat Resource Ctr, Birmingham, W Midlands, England; 7.Univ Fed Espirito Santo, Dept Pathol, Vitoria, ES, Brazil; 8.Univ Manchester, Christie Hosp, Manchester Acad Hlth Sci Ctr, Div Canc Sci, Manchester, Lancs, England; 9.Univ Birmingham, Inst Metab & Syst Res, Birmingham, W Midlands, England; 10.Univ Chicago Med, Chicago, IL USA; 11.Univ Texas Hlth Sci Ctr Houston, Dept Diagnost & Biomed Sci, Houston, TX 77030 USA; 12.Univ Birmingham, NIHR Birmingham Biomed Res Ctr, Birmingham, W Midlands, England; 13.Univ Hosp Birmingham NHS Fdn Trust, Birmingham, W Midlands, England
推荐引用方式 GB/T 7714	Brooks, Jill M.,Menezes, Albert N.,Ibrahim, Maha,et al. Development and Validation of a Combined Hypoxia and Immune Prognostic Classifier for Head and Neck Cancer[J],2019,25(17):5315-5328.
APA	Brooks, Jill M..,Menezes, Albert N..,Ibrahim, Maha.,Archer, Lucinda.,Lal, Neeraj.,...&Mehanna, Hisham.(2019).Development and Validation of a Combined Hypoxia and Immune Prognostic Classifier for Head and Neck Cancer.CLINICAL CANCER RESEARCH,25(17),5315-5328.
MLA	Brooks, Jill M.,et al."Development and Validation of a Combined Hypoxia and Immune Prognostic Classifier for Head and Neck Cancer".CLINICAL CANCER RESEARCH 25.17(2019):5315-5328.