Gene expression signatures modulated by epidermal growth factor receptor activation and their relationship to cetuximab resistance in head and neck squamous cell carcinoma
<p>Abstract</p> <p>Background</p> <p>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...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2012-05-01
|
| Series: | BMC Genomics |
| Online Access: | http://www.biomedcentral.com/1471-2164/13/160 |
| _version_ | 1811247664740696064 |
|---|---|
| author | Fertig Elana J Ren Qing Cheng Haixia Hatakeyama Hiromitsu Dicker Adam P Rodeck Ulrich Considine Michael Ochs Michael F Chung Christine H |
| author_facet | Fertig Elana J Ren Qing Cheng Haixia Hatakeyama Hiromitsu Dicker Adam P Rodeck Ulrich Considine Michael Ochs Michael F Chung Christine H |
| author_sort | Fertig Elana J |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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 HRAS<sup>Val12D</sup>.</p> <p>Results</p> <p>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-HRAS<sup>Val12D</sup> further associated with the cetuximab treatment response in isogenic cetuximab-sensitive (UMSCC1) and -resistant (1CC8) cell lines.</p> <p>Conclusions</p> <p>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.</p> |
| first_indexed | 2024-04-12T15:12:34Z |
| format | Article |
| id | doaj.art-f0df7572189d436591ede165890a2b99 |
| institution | Directory Open Access Journal |
| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-04-12T15:12:34Z |
| publishDate | 2012-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Genomics |
| spelling | doaj.art-f0df7572189d436591ede165890a2b992022-12-22T03:27:42ZengBMCBMC Genomics1471-21642012-05-0113116010.1186/1471-2164-13-160Gene expression signatures modulated by epidermal growth factor receptor activation and their relationship to cetuximab resistance in head and neck squamous cell carcinomaFertig Elana JRen QingCheng HaixiaHatakeyama HiromitsuDicker Adam PRodeck UlrichConsidine MichaelOchs Michael FChung Christine H<p>Abstract</p> <p>Background</p> <p>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 HRAS<sup>Val12D</sup>.</p> <p>Results</p> <p>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-HRAS<sup>Val12D</sup> further associated with the cetuximab treatment response in isogenic cetuximab-sensitive (UMSCC1) and -resistant (1CC8) cell lines.</p> <p>Conclusions</p> <p>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.</p>http://www.biomedcentral.com/1471-2164/13/160 |
| spellingShingle | Fertig Elana J Ren Qing Cheng Haixia Hatakeyama Hiromitsu Dicker Adam P Rodeck Ulrich Considine Michael Ochs Michael F Chung Christine H Gene expression signatures modulated by epidermal growth factor receptor activation and their relationship to cetuximab resistance in head and neck squamous cell carcinoma BMC Genomics |
| title | Gene expression signatures modulated by epidermal growth factor receptor activation and their relationship to cetuximab resistance in head and neck squamous cell carcinoma |
| title_full | Gene expression signatures modulated by epidermal growth factor receptor activation and their relationship to cetuximab resistance in head and neck squamous cell carcinoma |
| title_fullStr | Gene expression signatures modulated by epidermal growth factor receptor activation and their relationship to cetuximab resistance in head and neck squamous cell carcinoma |
| title_full_unstemmed | Gene expression signatures modulated by epidermal growth factor receptor activation and their relationship to cetuximab resistance in head and neck squamous cell carcinoma |
| title_short | Gene expression signatures modulated by epidermal growth factor receptor activation and their relationship to cetuximab resistance in head and neck squamous cell carcinoma |
| title_sort | gene expression signatures modulated by epidermal growth factor receptor activation and their relationship to cetuximab resistance in head and neck squamous cell carcinoma |
| url | http://www.biomedcentral.com/1471-2164/13/160 |
| work_keys_str_mv | AT fertigelanaj geneexpressionsignaturesmodulatedbyepidermalgrowthfactorreceptoractivationandtheirrelationshiptocetuximabresistanceinheadandnecksquamouscellcarcinoma AT renqing geneexpressionsignaturesmodulatedbyepidermalgrowthfactorreceptoractivationandtheirrelationshiptocetuximabresistanceinheadandnecksquamouscellcarcinoma AT chenghaixia geneexpressionsignaturesmodulatedbyepidermalgrowthfactorreceptoractivationandtheirrelationshiptocetuximabresistanceinheadandnecksquamouscellcarcinoma AT hatakeyamahiromitsu geneexpressionsignaturesmodulatedbyepidermalgrowthfactorreceptoractivationandtheirrelationshiptocetuximabresistanceinheadandnecksquamouscellcarcinoma AT dickeradamp geneexpressionsignaturesmodulatedbyepidermalgrowthfactorreceptoractivationandtheirrelationshiptocetuximabresistanceinheadandnecksquamouscellcarcinoma AT rodeckulrich geneexpressionsignaturesmodulatedbyepidermalgrowthfactorreceptoractivationandtheirrelationshiptocetuximabresistanceinheadandnecksquamouscellcarcinoma AT considinemichael geneexpressionsignaturesmodulatedbyepidermalgrowthfactorreceptoractivationandtheirrelationshiptocetuximabresistanceinheadandnecksquamouscellcarcinoma AT ochsmichaelf geneexpressionsignaturesmodulatedbyepidermalgrowthfactorreceptoractivationandtheirrelationshiptocetuximabresistanceinheadandnecksquamouscellcarcinoma AT chungchristineh geneexpressionsignaturesmodulatedbyepidermalgrowthfactorreceptoractivationandtheirrelationshiptocetuximabresistanceinheadandnecksquamouscellcarcinoma |