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dc.contributor.authorDemirkol Canlı, S.
dc.contributor.authorSeza, E. G.
dc.contributor.authorSheraj, I.
dc.contributor.authorGömçeli, İ.
dc.contributor.authorTurhan, N.
dc.contributor.authorCarberry, S.
dc.contributor.authorPrehn, J. H. M.
dc.contributor.authorGüre, Ali Osmay
dc.contributor.authorBanerjee, S.
dc.date.accessioned2021-02-26T06:35:49Z
dc.date.available2021-02-26T06:35:49Z
dc.date.issued2020-07
dc.identifier.issn0143-3334
dc.identifier.urihttp://hdl.handle.net/11693/75605
dc.description.abstractAKR1B1 and AKR1B10, members of the aldo-keto reductase family of enzymes that participate in the polyol pathway of aldehyde metabolism, are aberrantly expressed in colon cancer. We previously showed that high expression of AKR1B1 (AKR1B1HIGH) was associated with enhanced motility, inflammation and poor clinical outcome in colon cancer patients. Using publicly available datasets and ex vivo gene expression analysis (n = 51, Ankara cohort), we have validated our previous in silico finding that AKR1B1HIGH was associated with worse overall survival (OS) compared with patients with low expression of AKR1B1 (AKR1B1LOW) samples. A combined signature of AKR1B1HIGH and AKR1B10LOW was significantly associated with worse recurrence-free survival (RFS) in microsatellite stable (MSS) patients and in patients with distal colon tumors as well as a higher mesenchymal signature when compared with AKR1B1LOW/AKR1B10HIGH tumors. When the patients were stratified according to consensus molecular subtypes (CMS), AKR1B1HIGH/AKR1B10LOW samples were primarily classified as CMS4 with predominantly mesenchymal characteristics while AKR1B1LOW/AKR1B10HIGH samples were primarily classified as CMS3 which is associated with metabolic deregulation. Reverse Phase Protein Array carried out using protein samples from the Ankara cohort indicated that AKR1B1HIGH/AKR1B10LOW tumors showed aberrant activation of metabolic pathways. Western blot analysis of AKR1B1HIGH/AKR1B10LOW colon cancer cell lines also suggested aberrant activation of nutrient-sensing pathways. Collectively, our data suggest that the AKR1B1HIGH/AKR1B10LOW signature may be predictive of poor prognosis, aberrant activation of metabolic pathways, and can be considered as a novel biomarker for colon cancer prognostication.en_US
dc.language.isoEnglishen_US
dc.source.titleCarcinogenesisen_US
dc.relation.isversionofhttps://dx.doi.org/10.1093/carcin/bgaa072en_US
dc.subjectGene expressionen_US
dc.subjectWestern blottingen_US
dc.subjectCell linesen_US
dc.subjectColonic neoplasmsen_US
dc.subjectGene expression profilingen_US
dc.subjectOxidoreductaseen_US
dc.subjectRibosomal protein s6 kinaseen_US
dc.subjectNeoplasmsen_US
dc.subjectPatient prognosisen_US
dc.subjectConsensusen_US
dc.subjectEpithelial to mesenchymal transitionen_US
dc.subjectChromatographyen_US
dc.subjectReverse-phaseen_US
dc.subjectAldo-keto reductase family 1 member b10en_US
dc.subjectColorectal canceren_US
dc.titleEvaluation of an aldo-keto reductase gene signature with prognostic significance in colon cancer via activation of epithelial to mesenchymal transition and the p70S6K pathwayen_US
dc.typeArticleen_US
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.citation.spage1219en_US
dc.citation.epage1228en_US
dc.citation.volumeNumber41en_US
dc.citation.issueNumber9en_US
dc.identifier.doi10.1093/carcin/bgaa072en_US
dc.publisherOxford University Pressen_US
dc.contributor.bilkentauthorGüre, Ali Osmay


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