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dc.contributor.authorBriffa, Romina
dc.contributor.authorUm, In Hwa
dc.contributor.authorFaratian, Dana
dc.contributor.authorZhou, Ying
dc.contributor.authorTurnbull, Arran K
dc.contributor.authorLangdon, Simon P
dc.contributor.authorHarrison, David James
dc.date.accessioned2016-01-15T16:10:09Z
dc.date.available2016-01-15T16:10:09Z
dc.date.issued2015-12-17
dc.identifier.citationBriffa , R , Um , I H , Faratian , D , Zhou , Y , Turnbull , A K , Langdon , S P & Harrison , D J 2015 , ' Multi-scale genomic, transcriptomic and proteomic analysis of colorectal cancer cell lines to identify novel biomarkers ' PLoS One , vol. 10 , no. 12 , e0144708 . https://doi.org/10.1371/journal.pone.0144708en
dc.identifier.issn1932-6203
dc.identifier.otherPURE: 234874675
dc.identifier.otherPURE UUID: cad6de5b-00fa-4203-a625-6b62461b7df2
dc.identifier.otherScopus: 84956646500
dc.identifier.urihttp://hdl.handle.net/10023/8032
dc.descriptionThis work was partially funded by the Strategic Educational Pathways Scholarship (Malta). The scholarship is part-financed by the European Union – European Social Fund (ESF) under Operational Programme II – Cohesion Policy 2007-2013, “Empowering People for More Jobs and a Better Quality of Life”. This project was additionally funded by Medical Research Scotland.en
dc.description.abstractSelecting colorectal cancer (CRC) patients likely to respond to therapy remains a clinical challenge. The objectives of this study were to establish which genes were differentially expressed with respect to treatment sensitivity and relate this to copy number in a panel of 15 CRC cell lines. Copy number variations of the identified genes were assessed in a cohort of CRCs. IC50’s were measured for 5-fluorouracil, oxaliplatin, and BEZ-235, a PI3K/mTOR inhibitor. Cell lines were profiled using array comparative genomic hybridisation, Illumina gene expression analysis, reverse phase protein arrays, and targeted sequencing of KRAS hotspot mutations. Frequent gains were observed at 2p, 3q, 5p, 7p, 7q, 8q, 12p, 13q, 14q, and 17q and losses at 2q, 3p, 5q, 8p, 9p, 9q, 14q, 18q, and 20p. Frequently gained regions contained EGFR, PIK3CA, MYC, SMO, TRIB1, FZD1, and BRCA2, while frequently lost regions contained FHIT and MACROD2. TRIB1 was selected for further study. Gene enrichment analysis showed that differentially expressed genes with respect to treatment response were involved in Wnt signalling, EGF receptor signalling, apoptosis, cell cycle, and angiogenesis. Stepwise integration of copy number and gene expression data yielded 47 candidate genes that were significantly correlated. PDCD6 was differentially expressed in all three treatment responses. Tissue microarrays were constructed for a cohort of 118 CRC patients and TRIB1 and MYC amplifications were measured using fluorescence in situ hybridisation. TRIB1 and MYC were amplified in 14.5% and 7.4% of the cohort, respectively, and these amplifications were significantly correlated (p≤0.0001). TRIB1 protein expression in the patient cohort was significantly correlated with pERK, Akt, and Caspase 3 expression. In conclusion, a set of candidate predictive biomarkers for 5-fluorouracil, oxaliplatin, and BEZ235 are described that warrant further study. Amplification of the putative oncogene TRIB1 has been described for the first time in a cohort of CRC patients.en
dc.format.extent29en
dc.language.isoeng
dc.relation.ispartofPLoS Oneen
dc.rights© 2015 Briffa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en
dc.subjectRC0254 Neoplasms. Tumors. Oncology (including Cancer)en
dc.subjectRS Pharmacy and materia medicaen
dc.subjectNDASen
dc.subject.lccRC0254en
dc.subject.lccRSen
dc.titleMulti-scale genomic, transcriptomic and proteomic analysis of colorectal cancer cell lines to identify novel biomarkersen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews. School of Medicineen
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0144708
dc.description.statusPeer revieweden


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