title: Systematic Expression Analysis of Mitochondrial Complex I Identifies NDUFS1 as a Biomarker in Clear-Cell Renal-Cell Carcinoma.
abstract: Mitochondrial dysfunction is common in cancer, and the mitochondrial electron transport chain is often affected in carcinogenesis. So far, little is known about the expression of the mitochondrial complex I (NADH:ubiquinone oxidoreductase) subunits in clear-cell renal-cell carcinoma (ccRCC).
  
  
  
  An expression profile of the mitochondrial complex I subunits was determined using the NextBio database. Subsequently, the expression of selected subunits was experimentally validated on mRNA (quantitative real-time polymerase chain reaction) and protein (Western blot analysis, immunohistochemistry) level.
  
  
  
  We observed that 7 subunits of the complex I were down-regulated in at least 3 microarray studies. Deregulated mRNA expression was confirmed for NDUFA3, NDUFA, NDUFB1, NDUFB9, NDUFS1, NDUFS8, and NDUFV1. Low NDUFS1 mRNA expression was a significant and independent adverse predictor of a shorter overall survival in our mRNA cohort and the ccRCC cohort of The Cancer Genome Atlas project. NDUFS1 expression was furthermore analyzed on the protein level, and a distinct down-regulation was observed in ccRCC as well as in the chromophobe and the sarcomatoid subtype compared to normal renal tissue.
  
  
  
  Expression alterations occur in only a few subunits of the mitochondrial complex I subunits in ccRCC, and altered mRNA and protein expression levels of NDUFS1 may be useful to distinguish between renal-cell carcinoma and normal renal tissue.
authors.affiliation: Department of Urology, University Hospital Bonn, Bonn, Germany. Electronic address: joerg.ellinger@ukb.uni-bonn.de.
authors.forename: Jörg
authors.initials: J
authors.lastname: Ellinger
authors.affiliation: Department of Urology, University Hospital Bonn, Bonn, Germany.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Poss
authors.affiliation: Department of Urology, University Hospital Bonn, Bonn, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Brüggemann
authors.affiliation: Department of Urology, University Hospital Bonn, Bonn, Germany.
authors.forename: Arabella
authors.initials: A
authors.lastname: Gromes
authors.affiliation: Department of Urology, University Hospital Bonn, Bonn, Germany.
authors.forename: Doris
authors.initials: D
authors.lastname: Schmidt
authors.affiliation: Department of Anesthesiology and Intensive Care, University Hospital Bonn, Bonn, Germany.
authors.forename: Nadja
authors.initials: N
authors.lastname: Ellinger
authors.affiliation: Institute of Pathology, University Hospital Bonn, Bonn, Germany.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Tolkach
authors.affiliation: Institute of Pathology, University Hospital Bonn, Bonn, Germany; Department of Otorhinolaryngology/Head and Neck Surgery, University Hospital Bonn, Bonn, Germany.
authors.forename: Dimo
authors.initials: D
authors.lastname: Dietrich
authors.affiliation: Institute of Pathology, University Hospital Bonn, Bonn, Germany.
authors.forename: Glen
authors.initials: G
authors.lastname: Kristiansen
authors.affiliation: Department of Urology, University Hospital Bonn, Bonn, Germany.
authors.forename: Stefan C
authors.initials: SC
authors.lastname: Müller
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009245:NADH Dehydrogenase / Q000235:genetics* / Q000378:metabolism*; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; C487793:NDUFS1 protein, human; D009245:NADH Dehydrogenase
keywords: Biomarker; Expression profiling; Kidney; NDUFS1; Renal cell carcinoma