title: Piwi-interacting RNAs as novel prognostic markers in clear cell renal cell carcinomas.
abstract: BACKGROUND
  Piwi-interacting RNAs (piRNAs) are small RNAs of 27-30 nucleotides mapping to transposons or clustering in repeat genomic regions. Preliminary studies suggest an important role in cancerogenesis. This study is the first one investigating their prognostic impact in clear cell renal cell cancer (ccRCC) patients.
  
  
  METHODS
  Three piRNAs (piR-30924, piR-57125, and piR-38756) selected on the basis of initial piRNA microarray analyses were determined using RT-qPCR in non-metastatic (n = 76) and metastatic (n = 30) ccRCC tissue at the time of nephrectomy in comparison to normal renal tissue (n = 77) and tissue from distant ccRCC metastases (n = 13). Primary clinical end points were recurrence-free and overall survival.
  
  
  RESULTS
  piR-57125 showed lower expression in metastatic than in non-metastatic tumors, whereas the expression of piR-30924 and piR-38756 increased in metastatic tumors. The higher expression of piR-30924 and piR-38756 as well as the lower expression of piR-57125 in metastatic primary tumors were significantly associated with tumor recurrence and overall survival. Multivariate Cox regression analyses revealed both piR-30924 and piR-57125 as independent prognostic predictors. This impact was even more pronounced in non-metastatic patients.
  
  
  CONCLUSIONS
  This study demonstrates that the expression levels of these piRNAs in primary non-metastatic and metastatic ccRCC tissue can serve as potential prognostic biomarkers in combination with clinicopathological factors.
authors.affiliation: Department of Urology, Research Division, University Hospital Charité, Schumannstr. 20/12, 10117, Berlin, Germany. jonas.busch@charite.de.
authors.forename: Jonas
authors.initials: J
authors.lastname: Busch
authors.affiliation: Department of Urology, Research Division, University Hospital Charité, Schumannstr. 20/12, 10117, Berlin, Germany. bernhard.ralla@charite.de.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Ralla
authors.affiliation: Department of Urology, Research Division, University Hospital Charité, Schumannstr. 20/12, 10117, Berlin, Germany. monika.jung@charite.de.
authors.forename: Monika
authors.initials: M
authors.lastname: Jung
authors.affiliation: Department of Urology, Research Division, University Hospital Charité, Schumannstr. 20/12, 10117, Berlin, Germany. zofia.wot@gmail.com.|Berlin Institute for Urologic Research, Berlin, Germany. zofia.wot@gmail.com.
authors.forename: Zofia
authors.initials: Z
authors.lastname: Wotschofsky
authors.affiliation: Laboratorio clinico, Hospital Universitario Virgen Del Rocio, Sevilla, Spain. elenatrujilloarribas@gmail.com.
authors.forename: Elena
authors.initials: E
authors.lastname: Trujillo-Arribas
authors.affiliation: Center for Musculoskeletal Surgery, University Hospital Charité, Berlin, Germany. philipp.schwabe@charite.de.
authors.forename: Philipp
authors.initials: P
authors.lastname: Schwabe
authors.affiliation: Institute of Pathology, University Hospital Charité, Berlin, Germany. ergin.kilic@charite.de.
authors.forename: Ergin
authors.initials: E
authors.lastname: Kilic
authors.affiliation: Department of Urology, Research Division, University Hospital Charité, Schumannstr. 20/12, 10117, Berlin, Germany. annika.fendler@mdc-berlin.de.|Berlin Institute for Urologic Research, Berlin, Germany. annika.fendler@mdc-berlin.de.|Department of Signal Transduction, Invasion and Metastasis of Epithelial Cells, Max Delbrück Center of Molecular Medicine, Berlin, Germany. annika.fendler@mdc-berlin.de.
authors.forename: Annika
authors.initials: A
authors.lastname: Fendler
authors.affiliation: Department of Urology, Research Division, University Hospital Charité, Schumannstr. 20/12, 10117, Berlin, Germany. klaus.jung@charite.de.|Berlin Institute for Urologic Research, Berlin, Germany. klaus.jung@charite.de.
authors.forename: Klaus
authors.initials: K
authors.lastname: Jung
mesh_terms: D060565:Argonaute Proteins / Q000235:genetics* / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality; D005260:Female; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis; D011379:Prognosis; D034741:RNA, Small Interfering / Q000235:genetics; D016019:Survival Analysis
chemical_list: D060565:Argonaute Proteins; C421088:PIWIL1 protein, human; D034741:RNA, Small Interfering