gms | German Medical Science

62. Kongress der Nordrhein-Westfälischen Gesellschaft für Urologie

14. - 15.04.2016, Münster

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Identification of novel biomarkers in clear cell renal cell carcinoma

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  • presenting/speaker H. Miersch - Universitätsklinikum Bonn, Urologie, Bonn, Germany
  • J. Alam - Universitätsklinikum Bonn, Urologie, Bonn, Germany
  • N. Klümper - Universitätsklinikum Schleswig-Holstein, Institut für Pathologie, Lübeck, Germany
  • M. Deng - Universitätsklinikum Schleswig-Holstein, Institut für Pathologie, Lübeck, Germany
  • D. Schmidt - Universitätsklinikum Bonn, Urologie, Bonn, Germany
  • I. Syring - Universitätsklinikum Bonn, Urologie, Bonn, Germany
  • S. Perner - Universitätsklinikum Schleswig-Holstein, Institut für Pathologie, Lübeck, Germany
  • S.C. Müller - Universitätsklinikum Bonn, Urologie, Bonn, Germany
  • J. Ellinger - Universitätsklinikum Bonn, Urologie, Bonn, Germany

Nordrhein-Westfälische Gesellschaft für Urologie. 62. Kongress der Nordrhein-Westfälischen Gesellschaft für Urologie. Münster, 14.-15.04.2016. Düsseldorf: German Medical Science GMS Publishing House; 2016. DocV1.3

doi: 10.3205/16nrwgu12, urn:nbn:de:0183-16nrwgu127

Veröffentlicht: 25. Februar 2016

© 2016 Miersch et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.

Gliederung

Text

Purpose: Clear cell renal cell carcinoma (ccRCC) is among the most common human malignancies. In 2012 there were 115,200 new cases and 49,000 death estimated in Europe with increasing incidence, especially in young patients and high-grade disease. Up to now there are no diagnostic/prognostic biomarkers available for daily routine. The aim of this study was to identify such biomarkers.

Materials and methods: Therefore we evaluated a microarray dataset to identify differences between 34,144 mRNA transcripts in localized and advanced ccRCC. mRNAs with differential expression were then validated in an independent cohort using quantitative PCR, Western Blot and immunohistochemistry.

Results: We could observe 48 differential expressed mRNA transcripts in patients with localized and advanced ccRCC. 8 of them were not investigated by other researches so far. The expression of those was studied by qPCR. mRNAs with different expression in normal/malignant renal and localized/advanced ccRCC tissue were studied in a cohort of 50 normal renal, 57 localized ccRCC and 45 advanced ccRCC tissues. We observed an upregulation of PREX2 (10-fold; p< 0.001) and downregulation of ABCB8 (1.4-fold; p=0.001) in ccRCC compared to normal renal tissue. PDLIM7 was increased in advanced compared to localized ccRCC (5.1-fold; p=0.017) and normal renal tissue (9.1-fold; p=0.027). ABCB8 and NARS mRNA expression were also predictive of ccRCC patients' progression-free, cancer-specific and overall survival. We next confirmed the expression of these target genes on the protein level using a western blot. We observed a decrease of ABCB8-protein in tumor compared to normal renal tissue. In immunohistochemistry the expression of ABCB8 was decreased in ccRCC tissue compared to the proximal renal tubules (p< 0.001). Univariate Cox regression analysis showed that an increased ABCB8 immunostaining was correlated with poor cancer-specific survival.

Conclusions: We identified ABCB8 immunostaining as a predictive parameter for patients' outcome following nephrectomy.