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Expression parameters of the metabolic pathway genes pyruvate dehydrogenase kinase-1 (PDK-1) and DJ-1/PARK7 in renal cell carcinoma (RCC)

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Abstract

Purpose

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.

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Acknowledgments

We thank Waltraud Jekabsons and Antonia Maas for technical assistance with the experiments.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Urology, Universitätsklinikum Magdeburg A. ö. R., Leipziger Straße 44, 39104, Magdeburg, Germany

    Daniel Baumunk & Martin Schostak

  2. Department of Urology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin

    Jannis Hildebrandt, Hans Krause, Jan Ebbing, Hannes Cash, Kurt Miller & Steffen Weikert

  3. Department of Pathology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany

    Uta Reichelt

  4. Klinik für Urologie und Kinderurologie, Universitätsklinikum Magdeburg A. ö. R., Leipziger Straße 44, 39104, Magdeburg, Germany

    Daniel Baumunk

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  1. Daniel Baumunk
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Correspondence to Daniel Baumunk.

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Baumunk, D., Reichelt, U., Hildebrandt, J. et al. Expression parameters of the metabolic pathway genes pyruvate dehydrogenase kinase-1 (PDK-1) and DJ-1/PARK7 in renal cell carcinoma (RCC). World J Urol 31, 1191–1196 (2013). https://doi.org/10.1007/s00345-012-0874-5

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  • DOI: https://doi.org/10.1007/s00345-012-0874-5

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