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A systematic search strategy identifies cubilin as independent prognostic marker for renal cell carcinoma
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
Univ Edinburgh, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Inst Genet & Mol Med, Edinburgh Urol Canc Grp, Edinburgh, Midlothian, Scotland..
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2017 (English)In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 17, article id 9Article in journal (Refereed) Published
Abstract [en]

Background: 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.

Place, publisher, year, edition, pages
2017. Vol. 17, article id 9
Keyword [en]
Cubilin, Renal cell carcinoma, Independent prognostic biomarker, Immunohistochemistry
National Category
Cancer and Oncology Clinical Laboratory Medicine
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URN: urn:nbn:se:uu:diva-315058DOI: 10.1186/s12885-016-3030-6ISI: 000391341500003PubMedID: 28052770OAI: oai:DiVA.org:uu-315058DiVA, id: diva2:1078447
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Swedish Cancer SocietyKnut and Alice Wallenberg Foundation
Available from: 2017-03-03 Created: 2017-03-03 Last updated: 2017-11-29Bibliographically approved

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Gremel, GabrielaDjureinovic, DijanaNiinivirta, MarjutBergman, JuliaEdqvist, Per-Henrik DUllenhag, GustavPontén, Fredrik
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