title: Expression parameters of the metabolic pathway genes pyruvate dehydrogenase kinase-1 (PDK-1) and DJ-1/PARK7 in renal cell carcinoma (RCC).
abstract: OBJECTIVE
  Metabolic adaptations, such as increases in glucose and energy metabolism, play a pivotal role in the biology of RCC. PDK-1 and DJ-1/PARK7 are thought to control metabolic pathways in cancer. We investigated the expression of PDK-1 and DJ-1/PARK7 in RCC and their prognostic relevance.
  
  
  METHODS
  RCC tumor tissue and corresponding normal parenchyma samples were obtained from 91 patients with clear cell RCC. Expression of PDK-1 and DJ-1/PARK7 was determined on the mRNA and protein levels using quantitative RT-PCR and immunohistochemistry. Expression ratios tumor/normal were analyzed for associations with pathological stage and grade (Kruskal-Wallis ANOVA, chi-square test). Potential associations with progression-free and overall survival were analyzed using Cox regression models.
  
  
  RESULTS
  PDK-1 mRNA expression was up-regulated as compared to normal tissue (p < 0.001). Differences were observed by tumor stage (p < 0.05) with a trend toward lower expression with increasing stage (p > 0.01). Expression ratio tumor/normal also showed differences by tumor stage with the lowest ratio observed in advanced (pT3) disease. MRNA expression data were confirmed on the protein level with the lowest protein expression in pT3 tumors. PDK-1 expression ratio tumor/normal was inversely associated with outcome after adjustment for stage and grade (HR, 0.54; 95 % CI, 0.31-0.94). No associations observed for DJ-1/PARK7 expression.
  
  
  CONCLUSIONS
  PDK is up-regulated in RCC, but down-regulation may be associated with progression toward a metastasizing behavior. Given the role of PDK-1 in the control of glucose metabolism, aerobic glycolysis via up-regulation of PDK-1 may be an early event in RCC development, but less relevant for the progression toward an aggressive phenotype.
authors.affiliation: Department of Urology, Universitätsklinikum Magdeburg A. ö. R., Leipziger Straße 44, 39104, Magdeburg, Germany, daniel.baumunk@med.ovgu.de.
authors.forename: Daniel
authors.initials: D
authors.lastname: Baumunk
authors.forename: Uta
authors.initials: U
authors.lastname: Reichelt
authors.forename: Jannis
authors.initials: J
authors.lastname: Hildebrandt
authors.forename: Hans
authors.initials: H
authors.lastname: Krause
authors.forename: Jan
authors.initials: J
authors.lastname: Ebbing
authors.forename: Hannes
authors.initials: H
authors.lastname: Cash
authors.forename: Kurt
authors.initials: K
authors.lastname: Miller
authors.forename: Martin
authors.initials: M
authors.lastname: Schostak
authors.forename: Steffen
authors.initials: S
authors.lastname: Weikert
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D015536:Down-Regulation / Q000502:physiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics* / Q000502:physiology; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000473:pathology / Q000503:physiopathology; D009367:Neoplasm Staging; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism*; D011379:Prognosis; D000071617:Protein Deglycase DJ-1; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism*; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012189:Retrospective Studies; D015996:Survival Rate; D015854:Up-Regulation / Q000502:physiology
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D012333:RNA, Messenger; D017346:Protein Serine-Threonine Kinases; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1