{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1360002218968015488.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1186/1471-2164-13-160"}},{"identifier":{"@type":"PMID","@value":"22549044"}}],"resourceType":"学術雑誌論文(journal article)","dc:title":[{"@value":"Gene expression signatures modulated by epidermal growth factor receptor activation and their relationship to cetuximab resistance in head and neck squamous cell carcinoma"}],"description":[{"notation":[{"@value":"Aberrant activation of signaling pathways downstream of epidermal growth factor receptor (EGFR) has been hypothesized to be one of the mechanisms of cetuximab (a monoclonal antibody against EGFR) resistance in head and neck squamous cell carcinoma (HNSCC). To infer relevant and specific pathway activation downstream of EGFR from gene expression in HNSCC, we generated gene expression signatures using immortalized keratinocytes (HaCaT) subjected to ligand stimulation and transfected with EGFR, RELA/p65, or HRASVal12D.The gene expression patterns that distinguished the HaCaT variants and conditions were inferred using the Markov chain Monte Carlo (MCMC) matrix factorization algorithm Coordinated Gene Activity in Pattern Sets (CoGAPS). This approach inferred gene expression signatures with greater relevance to cell signaling pathway activation than the expression signatures inferred with standard linear models. Furthermore, the pathway signature generated using HaCaT-HRASVal12D further associated with the cetuximab treatment response in isogenic cetuximab-sensitive (UMSCC1) and -resistant (1CC8) cell lines.Our data suggest that the CoGAPS algorithm can generate gene expression signatures that are pertinent to downstream effects of receptor signaling pathway activation and potentially be useful in modeling resistance mechanisms to targeted therapies."}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380284922227338242","@type":"Researcher","foaf:name":[{"@value":"Elana J Fertig"}]},{"@id":"https://cir.nii.ac.jp/crid/1380284922227338241","@type":"Researcher","foaf:name":[{"@value":"Qing Ren"}]},{"@id":"https://cir.nii.ac.jp/crid/1380284922227338243","@type":"Researcher","foaf:name":[{"@value":"Haixia Cheng"}]},{"@id":"https://cir.nii.ac.jp/crid/1420845751136364928","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"10455652"},{"@type":"NRID","@value":"1000010455652"},{"@type":"NRID","@value":"9000267763405"},{"@type":"NRID","@value":"9000404130370"},{"@type":"NRID","@value":"9000391959719"},{"@type":"NRID","@value":"9000258079257"},{"@type":"NRID","@value":"9000259851454"},{"@type":"NRID","@value":"9000001138970"},{"@type":"NRID","@value":"9000296666686"},{"@type":"NRID","@value":"9000292872295"},{"@type":"NRID","@value":"9000402387242"},{"@type":"NRID","@value":"9000258078679"},{"@type":"NRID","@value":"9000258078461"},{"@type":"NRID","@value":"9000265536255"},{"@type":"NRID","@value":"9000237781685"},{"@type":"NRID","@value":"9000250177950"},{"@type":"NRID","@value":"9000329439306"},{"@type":"NRID","@value":"9000402783250"},{"@type":"NRID","@value":"9000396151780"},{"@type":"NRID","@value":"9000408891500"},{"@type":"NRID","@value":"9000267763414"},{"@type":"NRID","@value":"9000313202249"},{"@type":"NRID","@value":"9000331445086"},{"@type":"NRID","@value":"9000340953247"},{"@type":"NRID","@value":"9000380962761"},{"@type":"NRID","@value":"9000255719141"},{"@type":"NRID","@value":"9000258079736"},{"@type":"NRID","@value":"9000283513275"},{"@type":"NRID","@value":"9000336757167"},{"@type":"NRID","@value":"9000251399496"},{"@type":"NRID","@value":"9000283593023"},{"@type":"NRID","@value":"9000283513444"},{"@type":"NRID","@value":"9000334745961"},{"@type":"NRID","@value":"9000345404527"},{"@type":"NRID","@value":"9000250178016"},{"@type":"NRID","@value":"9000380962729"},{"@type":"NRID","@value":"9000377392212"},{"@type":"NRID","@value":"9000283515277"},{"@type":"NRID","@value":"9000398292780"},{"@type":"NRID","@value":"9000396151723"},{"@type":"NRID","@value":"9000256077608"},{"@type":"NRID","@value":"9000257921969"},{"@type":"NRID","@value":"9000397706801"},{"@type":"NRID","@value":"9000325470090"},{"@type":"NRID","@value":"9000370253273"},{"@type":"NRID","@value":"9000267763388"},{"@type":"NRID","@value":"9000336757152"},{"@type":"NRID","@value":"9000367410956"},{"@type":"NRID","@value":"9000391659007"},{"@type":"NRID","@value":"9000258078308"},{"@type":"NRID","@value":"9000340952665"},{"@type":"NRID","@value":"9000336037955"},{"@type":"NRID","@value":"9000309578282"},{"@type":"NRID","@value":"9000341093248"},{"@type":"NRID","@value":"9000292882414"},{"@type":"NRID","@value":"9000272998303"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/htkym"}],"foaf:name":[{"@value":"Hiromitsu Hatakeyama"}]},{"@id":"https://cir.nii.ac.jp/crid/1380284922227338240","@type":"Researcher","foaf:name":[{"@value":"Adam P Dicker"}]},{"@id":"https://cir.nii.ac.jp/crid/1380284922227338247","@type":"Researcher","foaf:name":[{"@value":"Ulrich Rodeck"}]},{"@id":"https://cir.nii.ac.jp/crid/1380284922227338248","@type":"Researcher","foaf:name":[{"@value":"Michael Considine"}]},{"@id":"https://cir.nii.ac.jp/crid/1380284922227338246","@type":"Researcher","foaf:name":[{"@value":"Michael F Ochs"}]},{"@id":"https://cir.nii.ac.jp/crid/1380284922227338245","@type":"Researcher","foaf:name":[{"@value":"Christine H Chung"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"14712164"}],"prism:publicationName":[{"@value":"BMC Genomics"}],"dc:publisher":[{"@value":"Springer Science and Business Media LLC"}],"prism:publicationDate":"2012","prism:volume":"13","prism:number":"1","prism:startingPage":"160"},"reviewed":"false","dcterms:accessRights":"http://purl.org/coar/access_right/c_abf2","createdAt":"2012-05-01","modifiedAt":"2016-05-16","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=Keratinocytes","dc:title":"Keratinocytes"},{"@id":"https://cir.nii.ac.jp/all?q=Drug%20Resistance","dc:title":"Drug Resistance"},{"@id":"https://cir.nii.ac.jp/all?q=Cetuximab","dc:title":"Cetuximab"},{"@id":"https://cir.nii.ac.jp/all?q=QH426-470","dc:title":"QH426-470"},{"@id":"https://cir.nii.ac.jp/all?q=Antibodies,%20Monoclonal,%20Humanized","dc:title":"Antibodies, Monoclonal, Humanized"},{"@id":"https://cir.nii.ac.jp/all?q=Antibodies","dc:title":"Antibodies"},{"@id":"https://cir.nii.ac.jp/all?q=Cell%20Line","dc:title":"Cell Line"},{"@id":"https://cir.nii.ac.jp/all?q=Cell%20Line,%20Tumor","dc:title":"Cell Line, Tumor"},{"@id":"https://cir.nii.ac.jp/all?q=Monoclonal","dc:title":"Monoclonal"},{"@id":"https://cir.nii.ac.jp/all?q=616","dc:title":"616"},{"@id":"https://cir.nii.ac.jp/all?q=Genetics","dc:title":"Genetics"},{"@id":"https://cir.nii.ac.jp/all?q=Humans","dc:title":"Humans"},{"@id":"https://cir.nii.ac.jp/all?q=Tumor","dc:title":"Tumor"},{"@id":"https://cir.nii.ac.jp/all?q=Epidermal%20Growth%20Factor","dc:title":"Epidermal Growth Factor"},{"@id":"https://cir.nii.ac.jp/all?q=Carcinoma","dc:title":"Carcinoma"},{"@id":"https://cir.nii.ac.jp/all?q=Antibodies,%20Monoclonal","dc:title":"Antibodies, Monoclonal"},{"@id":"https://cir.nii.ac.jp/all?q=ErbB%20Receptors","dc:title":"ErbB Receptors"},{"@id":"https://cir.nii.ac.jp/all?q=Squamous%20Cell","dc:title":"Squamous Cell"},{"@id":"https://cir.nii.ac.jp/all?q=Oncology","dc:title":"Oncology"},{"@id":"https://cir.nii.ac.jp/all?q=Drug%20Resistance,%20Neoplasm","dc:title":"Drug Resistance, Neoplasm"},{"@id":"https://cir.nii.ac.jp/all?q=Head%20and%20Neck%20Neoplasms","dc:title":"Head and Neck Neoplasms"},{"@id":"https://cir.nii.ac.jp/all?q=Carcinoma,%20Squamous%20Cell","dc:title":"Carcinoma, Squamous Cell"},{"@id":"https://cir.nii.ac.jp/all?q=Neoplasm","dc:title":"Neoplasm"},{"@id":"https://cir.nii.ac.jp/all?q=TP248.13-248.65","dc:title":"TP248.13-248.65"},{"@id":"https://cir.nii.ac.jp/all?q=Algorithms","dc:title":"Algorithms"},{"@id":"https://cir.nii.ac.jp/all?q=Receptor","dc:title":"Receptor"},{"@id":"https://cir.nii.ac.jp/all?q=Biotechnology","dc:title":"Biotechnology"},{"@id":"https://cir.nii.ac.jp/all?q=Research%20Article","dc:title":"Research Article"},{"@id":"https://cir.nii.ac.jp/all?q=Protein%20Binding","dc:title":"Protein Binding"},{"@id":"https://cir.nii.ac.jp/all?q=Signal%20Transduction","dc:title":"Signal Transduction"}],"project":[{"@id":"https://cir.nii.ac.jp/crid/1040000782169691264","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"23592517"},{"@type":"JGN","@value":"JP23592517"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23592517/"}],"notation":[{"@language":"ja","@value":"頭頸部癌シグナル伝達ネットワークの解明"},{"@language":"en","@value":"Network of signaling pathway of head and neck cancer"}]}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360011142933831296","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Cluster analysis and display of genome-wide expression patterns"}]},{"@id":"https://cir.nii.ac.jp/crid/1360011143504766336","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Head and Neck Cancer"}]},{"@id":"https://cir.nii.ac.jp/crid/1360292617911098624","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Hallmarks of Cancer: The Next Generation"}]},{"@id":"https://cir.nii.ac.jp/crid/1360292617912236672","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"A novel signaling pathway impact analysis"}]},{"@id":"https://cir.nii.ac.jp/crid/1360292619217457792","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Growth arrest of immortalized human keratinocytes and suppression of telomerase activity byp21WAF1 gene expression"}]},{"@id":"https://cir.nii.ac.jp/crid/1360292620631308800","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Pathway Analysis of Expression Data: Deciphering Functional Building Blocks of Complex Diseases"}]},{"@id":"https://cir.nii.ac.jp/crid/1360574092894061952","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Identification of Key Processes Underlying Cancer Phenotypes Using Biologic Pathway Analysis"}]},{"@id":"https://cir.nii.ac.jp/crid/1360574095603460992","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Determination of strongly overlapping signaling activity from microarray data"}]},{"@id":"https://cir.nii.ac.jp/crid/1360574096453645184","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Decreased Growth Inhibitory Responses of Squamous Carcinoma Cells to Interferon-γ Involve Failure to Recruit cki Proteins into cdk2 Complexes"}]},{"@id":"https://cir.nii.ac.jp/crid/1360574096512370560","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Frozen robust multiarray analysis (fRMA)"}]},{"@id":"https://cir.nii.ac.jp/crid/1360855224121747328","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Inference of patient-specific pathway activities from multi-dimensional cancer genomics data using PARADIGM"}]},{"@id":"https://cir.nii.ac.jp/crid/1360855569147443072","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Regulation of Heparin-Binding EGF-Like Growth Factor by miR-212 and Acquired Cetuximab-Resistance in Head and Neck Squamous Cell Carcinoma"}]},{"@id":"https://cir.nii.ac.jp/crid/1360855569253310976","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Complex Regulation of Signal Transducers and Activators of Transcription 3 Activation in Normal and Malignant Keratinocytes"}]},{"@id":"https://cir.nii.ac.jp/crid/1360855570945988224","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Normal keratinization in a spontaneously immortalized aneuploid human keratinocyte cell line."}]},{"@id":"https://cir.nii.ac.jp/crid/1360855571423125888","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"CoGAPS: an R/C++ package to identify patterns and biological process activity in transcriptomic data"}]},{"@id":"https://cir.nii.ac.jp/crid/1361137045846442752","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Prior Distributions on Measure Space"}]},{"@id":"https://cir.nii.ac.jp/crid/1361418519150707968","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"TGFβ signaling in head and neck squamous cell carcinoma"}]},{"@id":"https://cir.nii.ac.jp/crid/1361418519375762304","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"ErbB receptors in the biology and pathology of the aerodigestive tract"}]},{"@id":"https://cir.nii.ac.jp/crid/1361418519522683520","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"ASAP: automated sequence annotation pipeline for\nweb-based updating of sequence information with a local dynamic\ndatabase"}]},{"@id":"https://cir.nii.ac.jp/crid/1361418520815961856","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Singular value decomposition for genome-wide expression data processing and modeling"}]},{"@id":"https://cir.nii.ac.jp/crid/1361699993716826624","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Platinum-Based Chemotherapy plus Cetuximab in Head and Neck Cancer"}]},{"@id":"https://cir.nii.ac.jp/crid/1361699994285217280","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"p53 Mutations in human immortalized epithelial cell lines"}]},{"@id":"https://cir.nii.ac.jp/crid/1361981468575948800","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Malignant Transformation of Immortalized HaCaT Keratinocytes through Deregulated Nuclear Factor κB Signaling"}]},{"@id":"https://cir.nii.ac.jp/crid/1361981468630399744","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Bayesian Decomposition: Analyzing Microarray Data within a Biological Context"}]},{"@id":"https://cir.nii.ac.jp/crid/1361981471216548992","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Application of Bayesian Decomposition for analysing microarray\n  data"}]},{"@id":"https://cir.nii.ac.jp/crid/1362544418426571264","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Radiotherapy plus Cetuximab for Squamous-Cell Carcinoma of the Head and Neck"}]},{"@id":"https://cir.nii.ac.jp/crid/1362544418865440768","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Exome Sequencing of Head and Neck Squamous Cell Carcinoma Reveals Inactivating Mutations in\n                    <i>NOTCH1</i>"}]},{"@id":"https://cir.nii.ac.jp/crid/1363107370170660864","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Epidermal Growth Factor Receptor-dependent Control of Keratinocyte Survival and Bcl-xL Expression through a MEK-dependent Pathway"}]},{"@id":"https://cir.nii.ac.jp/crid/1363107370372769920","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Targeting RAS signalling pathways in cancer therapy"}]},{"@id":"https://cir.nii.ac.jp/crid/1363388843421662592","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"A Model for Measurement Error for Gene Expression Arrays"}]},{"@id":"https://cir.nii.ac.jp/crid/1363388844491892224","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Detection of Treatment-Induced Changes in Signaling Pathways in Gastrointestinal Stromal Tumors Using Transcriptomic Data"}]},{"@id":"https://cir.nii.ac.jp/crid/1363670318488290816","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Targeting EGFR resistance networks in head and neck cancer"}]},{"@id":"https://cir.nii.ac.jp/crid/1363670321235891328","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Molecular classification of head and neck squamous cell carcinomas using patterns of gene expression"}]},{"@id":"https://cir.nii.ac.jp/crid/1363951794445302784","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"The Mutational Landscape of Head and Neck Squamous Cell Carcinoma"}]},{"@id":"https://cir.nii.ac.jp/crid/1363951795253290752","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Phase II Trial of ZD1839 in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1186/1471-2164-13-160"},{"@type":"KAKEN","@value":"PRODUCT-14190783"},{"@type":"KAKEN","@value":"PRODUCT-14190768"},{"@type":"OPENAIRE","@value":"doi_dedup___::c6ab019c76eff31e6b9bbc8ad4a2ea53"}]}