title: Reduced mRNA expression level of corticotropin-releasing hormone-binding protein is associated with aggressive human kidney cancer.
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.
authors.affiliation: Department of Urology and Urological Oncology, Hannover Medical School, Hannover, Germany. tezval.hossein@mh-hannover.de
authors.forename: Hossein
authors.initials: H
authors.lastname: Tezval
authors.forename: Faranaz
authors.initials: F
authors.lastname: Atschekzei
authors.forename: Inga
authors.initials: I
authors.lastname: Peters
authors.forename: Sandra
authors.initials: S
authors.lastname: Waalkes
authors.forename: Jörg
authors.initials: J
authors.lastname: Hennenlotter
authors.forename: Arnulf
authors.initials: A
authors.lastname: Stenzl
authors.forename: Jan U
authors.initials: JU
authors.lastname: Becker
authors.forename: Axel S
authors.initials: AS
authors.lastname: Merseburger
authors.forename: Markus A
authors.initials: MA
authors.lastname: Kuczyk
authors.forename: Jürgen
authors.initials: J
authors.lastname: Serth
mesh_terms: D000368:Aged; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism / Q000556:secondary*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D007678:Kidney Glomerulus / Q000378:metabolism; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D007687:Kidney Tubules, Proximal / Q000378:metabolism; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D012333:RNA, Messenger; C067133:corticotropin releasing factor-binding protein