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Open Access Research article

Reduced mrna expression level of corticotropin-releasing hormone-binding protein is associated with aggressive human kidney cancer

Hossein Tezval1*, Faranaz Atschekzei1, Inga Peters1, Sandra Waalkes1, Jörg Hennenlotter2, Arnulf Stenzl2, Jan U Becker3, Axel S Merseburger1, Markus A Kuczyk1 and Jürgen Serth1

Author Affiliations

1 Department of Urology and Urological Oncology, Hannover Medical School, Hannover, Germany

2 Department of Urology, Eberhard Karls University of Tuebingen, Tuebingen, Germany

3 Institute of Pathology, Hannover Medical School, Hannover, Germany

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BMC Cancer 2013, 13:199  doi:10.1186/1471-2407-13-199

Published: 22 April 2013

Abstract

Background

Significance of Urocortin (Ucn or UcnI), Ucn2, Ucn3 and their receptors, Corticotropin Releasing Factor Receptor 1 and 2 (CRFR1 and CRFR2), and the binding protein, Corticotropin-Releasing Hormone-Binding Protein (CRHBP) in oncology is growing rapidly. The objective of our study was to assess the expression of the CRHBP mRNA and protein in renal cancer.

Methods

Tumoral tissues of 78 patients with clear cell renal cell cancer and their corresponding normal tissues were analyzed using quantitative mRNA expression analysis for detection of mRNA expression level. Protein expression and tissue localization of CRHBP protein in renal specimens was evaluated using western blotting, immunohistochemistry and double immunofluorescence, respectively.

Results

We found an approx. 33 fold decrease of average CRHBP mRNA level in tumoral tissues compared to paired normal tissues (p<0.001). Diminished CRHBP mRNA expression was positively correlated with advanced, metastasized and higher stage of disease (p<0.001, p=0.026, p=0.028 respectively). CRHBP protein was detected in glomeruli and proximal tubules of normal kidney while none or weak immunopositivity was found in cc-RCC (p<0.001).

Conclusions

The expression analysis of CRHBP shows that cc-RCC is characterized by a significant loss of CRHBP mRNA expression that furthermore is associated with a more aggressive state of tumors. Depletion of CRHBP proteins also indicate that the protein as part of the UCN system may be involved in renal carcinogenesis.