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A systematic search strategy identifies cubilin as independent prognostic marker for renal cell carcinoma

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Date
04/01/2017
Author
Gremel, Gabriela
Djureinovic, Dijana
Niinivirta, Marjut
Laird, Alexander
Ljungqvist, Oscar
Johannesson, Henrik
Bergman, Julia
Edqvist, Perk-Henrik
Navani, Sanjay
Khan, Naila
Patil, Tushar
Sivertsson, Åsa
Uhlén, Mathias
Harrison, David James
Ullenhag, Gustav J.
Stewart, Grant D.
Pontén, Fredrik
Keywords
Cubilin
Renal cell carcinoma
Independent prognostic biomarker
Immunohistochemistry
QA75 Electronic computers. Computer science
RB Pathology
RC0254 Neoplasms. Tumors. Oncology (including Cancer)
NDAS
SDG 3 - Good Health and Well-being
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Abstract
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.
Citation
Gremel , 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/s12885-016-3030-6
Publication
BMC Cancer
Status
Peer reviewed
DOI
https://doi.org/10.1186/s12885-016-3030-6
ISSN
1471-2407
Type
Journal article
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 stated
Description
This 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.
Collections
  • University of St Andrews Research
URI
http://hdl.handle.net/10023/10047

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