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Published on: January 7, 2013
Systematic Expression Analysis of Mitochondrial Complex I Identifies NDUFS1 as a Biomarker in Clear-Cell Renal-Cell
Jörg Ellinger1, Mirjam Poss1, Maria Brüggemann1
1Department of Urology, University Hospital Bonn, Bonn, Germany.
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.
Insights
Mitochondrial complex I subunit NDUFS1 is down-regulated in clear-cell renal-cell carcinoma (ccRCC). Low NDUFS1 levels predict shorter survival and may help differentiate ccRCC from normal tissue.
Area of Science:
- Oncology
- Molecular Biology
- Mitochondrial Biology
Background:
- Mitochondrial dysfunction is prevalent in cancer, impacting the electron transport chain.
- The expression of mitochondrial complex I subunits in clear-cell renal-cell carcinoma (ccRCC) remains largely uncharacterized.
Purpose of the Study:
- To investigate the expression profile of mitochondrial complex I subunits in ccRCC.
- To determine the prognostic significance of NDUFS1 expression in ccRCC.
Main Methods:
- Utilized the NextBio database for expression profiling of mitochondrial complex I subunits.
- Validated mRNA and protein expression of selected subunits using quantitative real-time polymerase chain reaction, Western blot analysis, and immunohistochemistry.
Main Results:
- Seven mitochondrial complex I subunits were found to be down-regulated in ccRCC across multiple microarray studies.
- Down-regulated mRNA expression was confirmed for NDUFA3, NDUFA, NDUFB1, NDUFB9, NDUFS1, NDUFS8, and NDUFV1.
- Low NDUFS1 mRNA expression was an independent predictor of shorter overall survival in ccRCC cohorts. Protein analysis revealed NDUFS1 down-regulation in ccRCC and its subtypes compared to normal renal tissue.
Conclusions:
- Expression alterations in mitochondrial complex I subunits are limited in ccRCC.
- Altered NDUFS1 mRNA and protein expression may serve as a biomarker for distinguishing ccRCC from normal renal tissue.
