STAT3-dependent analysis reveals PDK4 as independent predictor of recurrence in prostate cancer.

Autor: Oberhuber M; Department of Pathology, Medical University of Vienna, Vienna, Austria.; CBmed-Center for Biomarker Research in Medicine GmbH, Graz, Austria., Pecoraro M; Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany., Rusz M; Department of Analytical Chemistry, University of Vienna, Vienna, Austria.; Institute of Inorganic Chemistry, University of Vienna, Vienna, Austria., Oberhuber G; Patho im Zentrum, St.Pölten, Austria., Wieselberg M; Department of Pathology, Medical University of Vienna, Vienna, Austria.; CBmed-Center for Biomarker Research in Medicine GmbH, Graz, Austria., Haslinger P; Department of Obstetrics and Gynaecology, Medical University of Vienna, Vienna, Austria., Gurnhofer E; Department of Pathology, Medical University of Vienna, Vienna, Austria., Schlederer M; Department of Pathology, Medical University of Vienna, Vienna, Austria., Limberger T; Department of Pathology, Medical University of Vienna, Vienna, Austria., Lagger S; Unit of Pathology of Laboratory Animals, University of Veterinary Medicine Vienna, Vienna, Austria., Pencik J; Department of Pathology, Medical University of Vienna, Vienna, Austria.; CBmed-Center for Biomarker Research in Medicine GmbH, Graz, Austria., Kodajova P; Unit of Pathology of Laboratory Animals, University of Veterinary Medicine Vienna, Vienna, Austria., Högler S; Unit of Pathology of Laboratory Animals, University of Veterinary Medicine Vienna, Vienna, Austria., Stockmaier G; Department of Biosciences, University of Salzburg, Salzburg, Austria., Grund-Gröschke S; Department of Biosciences, University of Salzburg, Salzburg, Austria., Aberger F; Department of Biosciences, University of Salzburg, Salzburg, Austria., Bolis M; Institute of Oncology Research (IOR), Bellinzona, Switzerland.; Università delle Svizzera italiana, Lugano, Switzerland., Theurillat JP; Institute of Oncology Research (IOR), Bellinzona, Switzerland.; Università delle Svizzera italiana, Lugano, Switzerland., Wiebringhaus R; Department of Pathology, Medical University of Vienna, Vienna, Austria., Weiss T; Department of Pathology, Medical University of Vienna, Vienna, Austria.; CBmed-Center for Biomarker Research in Medicine GmbH, Graz, Austria., Haitel A; Department of Pathology, Medical University of Vienna, Vienna, Austria., Brehme M; CBmed-Center for Biomarker Research in Medicine GmbH, Graz, Austria., Wadsak W; CBmed-Center for Biomarker Research in Medicine GmbH, Graz, Austria.; Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria., Griss J; Department of Dermatology, Medical University of Vienna, Vienna, Austria., Mohr T; Department of Medicine I, Medical University of Vienna, Vienna, Austria.; Science Consult DI, Thomas Mohr KG, Guntramsdorf, Austria., Hofer A; Research Area Biochemical Engineering, Institute of Chemical, Environmental and Biological Engineering, Vienna University of Technology, Vienna, Austria., Jäger A; Department of Pathology, Medical University of Vienna, Vienna, Austria., Pollheimer J; Department of Obstetrics and Gynaecology, Medical University of Vienna, Vienna, Austria., Egger G; Department of Pathology, Medical University of Vienna, Vienna, Austria.; Ludwig Boltzmann Institute Applied Diagnostics, Vienna, Austria., Koellensperger G; Department of Analytical Chemistry, University of Vienna, Vienna, Austria., Mann M; Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany., Hantusch B; Department of Pathology, Medical University of Vienna, Vienna, Austria., Kenner L; Department of Pathology, Medical University of Vienna, Vienna, Austria.; CBmed-Center for Biomarker Research in Medicine GmbH, Graz, Austria.; Unit of Pathology of Laboratory Animals, University of Veterinary Medicine Vienna, Vienna, Austria.; Christian Doppler Laboratory for Applied Metabolomics (CDL AM), Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria.; Ludwig Boltzmann Platform for Comparative Laboratory Animal Pathology, Vienna, Austria.
Jazyk: angličtina
Zdroj: Molecular systems biology [Mol Syst Biol] 2020 Apr; Vol. 16 (4), pp. e9247.
DOI: 10.15252/msb.20199247
Abstrakt: Prostate cancer (PCa) has a broad spectrum of clinical behavior; hence, biomarkers are urgently needed for risk stratification. Here, we aim to find potential biomarkers for risk stratification, by utilizing a gene co-expression network of transcriptomics data in addition to laser-microdissected proteomics from human and murine prostate FFPE samples. We show up-regulation of oxidative phosphorylation (OXPHOS) in PCa on the transcriptomic level and up-regulation of the TCA cycle/OXPHOS on the proteomic level, which is inversely correlated to STAT3 expression. We hereby identify gene expression of pyruvate dehydrogenase kinase 4 (PDK4), a key regulator of the TCA cycle, as a promising independent prognostic marker in PCa. PDK4 predicts disease recurrence independent of diagnostic risk factors such as grading, staging, and PSA level. Therefore, low PDK4 is a promising marker for PCa with dismal prognosis.
(© 2020 The Authors. Published under the terms of the CC BY 4.0 license.)
Databáze: MEDLINE
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