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dc.contributor.authorDemirkol, S.en_US
dc.contributor.authorGomceli, I.en_US
dc.contributor.authorIsbilen, M.en_US
dc.contributor.authorDayanc, B. E.en_US
dc.contributor.authorTez, M.en_US
dc.contributor.authorBostanci, E. B.en_US
dc.contributor.authorTurhan, N.en_US
dc.contributor.authorAkoglu, M.en_US
dc.contributor.authorOzyerli, E.en_US
dc.contributor.authorDurdu, S.en_US
dc.contributor.authorKonu, O.en_US
dc.contributor.authorNissan, A.en_US
dc.contributor.authorGonen, M.en_US
dc.contributor.authorGure, A. O.en_US
dc.date.accessioned2018-04-12T10:59:23Z
dc.date.available2018-04-12T10:59:23Z
dc.date.issued2017en_US
dc.identifier.issn1837-9664
dc.identifier.urihttp://hdl.handle.net/11693/36992
dc.description.abstractBackground: Prognostic biomarkers for cancer have the power to change the course of disease if they add value beyond known prognostic factors, if they can help shape treatment protocols, and if they are reliable. The aim of this study was to identify such biomarkers for colon cancer and to understand the molecular mechanisms leading to prognostic stratifications based on these biomarkers. Methods and Findings: We used an in house R based script (SSAT) for the in silico discovery of stage-independent prognostic biomarkers using two cohorts, GSE17536 and GSE17537, that include 177 and 55 colon cancer patients, respectively. This identified 2 genes, ULBP2 and SEMA5A, which when used jointly, could distinguish patients with distinct prognosis. We validated our findings using a third cohort of 48 patients ex vivo. We find that in all cohorts, a combined ULBP2/SEMA5A classification (SU-GIB) can stratify distinct prognostic sub-groups with hazard ratios that range from 2.4 to 4.5 (p=0.01) when overall- or cancer-specific survival is used as an end-measure, independent of confounding prognostic parameters. In addition, our preliminary analyses suggest SU-GIB is comparable to Oncotype DX colon(®) in predicting recurrence in two different cohorts (HR: 1.5-2; p=0.02). SU-GIB has potential as a companion diagnostic for several drugs including the PI3K/mTOR inhibitor BEZ235, which are suitable for the treatment of patients within the bad prognosis group. We show that tumors from patients with worse prognosis have low EGFR autophosphorylation rates, but high caspase 7 activity, and show upregulation of pro-inflammatory cytokines that relate to a relatively mesenchymal phenotype. Conclusions: We describe two novel genes that can be used to prognosticate colon cancer and suggest approaches by which such tumors can be treated. We also describe molecular characteristics of tumors stratified by the SU-GIB signature.en_US
dc.language.isoEnglishen_US
dc.source.titleJournal of Canceren_US
dc.relation.isversionofhttps://.doi.org/10.7150/jca.17872en_US
dc.subjectBiomarkeren_US
dc.subjectColon canceren_US
dc.subjectPrognosisen_US
dc.subjectBiological markeren_US
dc.subjectCaspase 7en_US
dc.subjectDactolisiben_US
dc.subjectEpidermal growth factor receptoren_US
dc.subjectProtein derivativeen_US
dc.subjectProtein sema5aen_US
dc.subjectProtein ULBP2en_US
dc.subjectUnclassified drugen_US
dc.subjectAdulten_US
dc.subjectAgeden_US
dc.subjectAutophosphorylationen_US
dc.subjectCancer prognosisen_US
dc.subjectCancer recurrenceen_US
dc.subjectCancer specific survivalen_US
dc.subjectColon canceren_US
dc.subjectEnzyme activityen_US
dc.subjectFemaleen_US
dc.subjectHumanen_US
dc.subjectHuman tissueen_US
dc.subjectMajor clinical studyen_US
dc.subjectMaleen_US
dc.subjectMicrosatellite instabilityen_US
dc.subjectOverall survivalen_US
dc.subjectProtein expressionen_US
dc.subjectUpregulationen_US
dc.titleA combined ULBP2 and SEMA5A expression signature as a prognostic and predictive biomarker for colon canceren_US
dc.typeArticleen_US
dc.departmentDepartment of Molecular Biology and Genetics
dc.citation.spage1113en_US
dc.citation.epage1122en_US
dc.citation.volumeNumber8en_US
dc.citation.issueNumber7en_US
dc.identifier.doi10.7150/jca.17872en_US
dc.publisherIvyspring International Publisheren_US


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