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dc.contributor.authorGremel, Gabriela
dc.contributor.authorDjureinovic, Dijana
dc.contributor.authorNiinivirta, Marjut
dc.contributor.authorLaird, Alexander
dc.contributor.authorLjungqvist, Oscar
dc.contributor.authorJohannesson, Henrik
dc.contributor.authorBergman, Julia
dc.contributor.authorEdqvist, Perk-Henrik
dc.contributor.authorNavani, Sanjay
dc.contributor.authorKhan, Naila
dc.contributor.authorPatil, Tushar
dc.contributor.authorSivertsson, Åsa
dc.contributor.authorUhlén, Mathias
dc.contributor.authorHarrison, David James
dc.contributor.authorUllenhag, Gustav J.
dc.contributor.authorStewart, Grant D.
dc.contributor.authorPontén, Fredrik
dc.date.accessioned2017-01-05T12:30:14Z
dc.date.available2017-01-05T12:30:14Z
dc.date.issued2017-01-04
dc.identifier.citationGremel , G , Djureinovic , D , Niinivirta , M , Laird , A , Ljungqvist , O , Johannesson , H , Bergman , J , Edqvist , P-H , Navani , S , Khan , N , Patil , T , Sivertsson , Å , Uhlén , M , Harrison , D J , Ullenhag , G J , Stewart , G D & Pontén , F 2017 , ' A systematic search strategy identifies cubilin as independent prognostic marker for renal cell carcinoma ' , BMC Cancer , vol. 17 , 9 . https://doi.org/10.1186/s12885-016-3030-6en
dc.identifier.issn1471-2407
dc.identifier.otherPURE: 248482316
dc.identifier.otherPURE UUID: 292a06f2-b670-4b85-b7bc-bc5a4b3661ee
dc.identifier.otherScopus: 85008151958
dc.identifier.otherWOS: 000391341500003
dc.identifier.otherORCID: /0000-0001-9041-9988/work/64034309
dc.identifier.urihttps://hdl.handle.net/10023/10047
dc.descriptionThis work was supported by the Swedish Cancer Society and the Knut and Alice Wallenberg Foundation. The work of DJH and GDS was funded by the Chief Scientist Office (grant number ETM37), Renal Cancer Research Fund and Kidney Cancer Scotland.en
dc.description.abstractBackground There is an unmet clinical need for better prognostic and diagnostic tools for renal cell carcinoma (RCC). Methods Human Protein Atlas data resources, including the transcriptomes and proteomes of normal and malignant human tissues, were searched for RCC-specific proteins and cubilin (CUBN) identified as a candidate. Patient tissue representing various cancer types was constructed into a tissue microarray (n = 940) and immunohistochemistry used to investigate the specificity of CUBN expression in RCC as compared to other cancers. Two independent RCC cohorts (n = 181; n = 114) were analyzed to further establish the sensitivity of CUBN as RCC-specific marker and to explore if the fraction of RCCs lacking CUBN expression could predict differences in patient survival. Results CUBN was identified as highly RCC-specific protein with 58% of all primary RCCs staining positive for CUBN using immunohistochemistry. In venous tumor thrombi and metastatic lesions, the frequency of CUBN expression was increasingly lost. Clear cell RCC (ccRCC) patients with CUBN positive tumors had a significantly better prognosis compared to patients with CUBN negative tumors, independent of T-stage, Fuhrman grade and nodal status (HR 0.382, CI 0.203–0.719, P = 0.003). Conclusions CUBN expression is highly specific to RCC and loss of the protein is significantly and independently associated with poor prognosis. CUBN expression in ccRCC provides a promising positive prognostic indicator for patients with ccRCC. The high specificity of CUBN expression in RCC also suggests a role as a new diagnostic marker in clinical cancer differential diagnostics to confirm or rule out RCC.
dc.format.extent9
dc.language.isoeng
dc.relation.ispartofBMC Canceren
dc.rights© The Author(s). 2017 This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stateden
dc.subjectCubilinen
dc.subjectRenal cell carcinomaen
dc.subjectIndependent prognostic biomarkeren
dc.subjectImmunohistochemistryen
dc.subjectQA75 Electronic computers. Computer scienceen
dc.subjectRB Pathologyen
dc.subjectRC0254 Neoplasms. Tumors. Oncology (including Cancer)en
dc.subjectNDASen
dc.subjectSDG 3 - Good Health and Well-beingen
dc.subject.lccQA75en
dc.subject.lccRBen
dc.subject.lccRC0254en
dc.titleA systematic search strategy identifies cubilin as independent prognostic marker for renal cell carcinomaen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews. School of Medicineen
dc.contributor.institutionUniversity of St Andrews. Cellular Medicine Divisionen
dc.identifier.doihttps://doi.org/10.1186/s12885-016-3030-6
dc.description.statusPeer revieweden


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