Systematic Expression Analysis of Mitochondrial Complex I Identifies NDUFS1 as a Biomarker in Clear-Cell Renal-Cell Carcinoma
| Autor: | Arabella Gromes, Stefan C. Müller, Nadja Ellinger, Mirjam Poss, Doris Schmidt, Maria Brüggemann, Dimo Dietrich, Glen Kristiansen, Jörg Ellinger, Yuri Tolkach |
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| Rok vydání: | 2017 |
| Předmět: |
Adult
Male 0301 basic medicine Urology Down-Regulation NDUFV1 Biology medicine.disease_cause 03 medical and health sciences Biomarkers Tumor medicine Humans Carcinoma Renal Cell Aged Neoplasm Staging Aged 80 and over Messenger RNA NDUFS8 NDUFS1 NADH Dehydrogenase Middle Aged Prognosis medicine.disease Survival Analysis NDUFB9 Molecular biology Kidney Neoplasms Gene Expression Regulation Neoplastic Gene expression profiling Clear cell renal cell carcinoma 030104 developmental biology Oncology Female Neoplasm Grading Carcinogenesis |
| Zdroj: | Clinical Genitourinary Cancer. 15:e551-e562 |
| ISSN: | 1558-7673 |
| DOI: | 10.1016/j.clgc.2016.11.010 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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