Jörg Ellinger1, Mirjam Poss2, Maria Brüggemann2, Arabella Gromes2, Doris Schmidt2, Nadja Ellinger3, Yuri Tolkach4, Dimo Dietrich5, Glen Kristiansen4, Stefan C Müller2. 1. Department of Urology, University Hospital Bonn, Bonn, Germany. Electronic address: joerg.ellinger@ukb.uni-bonn.de. 2. Department of Urology, University Hospital Bonn, Bonn, Germany. 3. Department of Anesthesiology and Intensive Care, University Hospital Bonn, Bonn, Germany. 4. Institute of Pathology, University Hospital Bonn, Bonn, Germany. 5. Institute of Pathology, University Hospital Bonn, Bonn, Germany; Department of Otorhinolaryngology/Head and Neck Surgery, University Hospital Bonn, Bonn, Germany.
Abstract
INTRODUCTION: 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). MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.
INTRODUCTION: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). MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.
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