Abstract

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.

Details

Title
STAT 3 ‐dependent analysis reveals PDK 4 as independent predictor of recurrence in prostate cancer
Author
Oberhuber, Monika 1   VIAFID ORCID Logo  ; Pecoraro, Matteo 2 ; Rusz, Mate 3   VIAFID ORCID Logo  ; Oberhuber, Georg 4 ; Wieselberg, Maritta 1 ; Haslinger, Peter 5   VIAFID ORCID Logo  ; Gurnhofer, Elisabeth 6   VIAFID ORCID Logo  ; Schlederer, Michaela 6 ; Limberger, Tanja 6   VIAFID ORCID Logo  ; Lagger, Sabine 7   VIAFID ORCID Logo  ; Pencik, Jan 1 ; Kodajova, Petra 7   VIAFID ORCID Logo  ; Högler, Sandra 7   VIAFID ORCID Logo  ; Stockmaier, Georg 8 ; Sandra Grund‐Gröschke 8 ; Aberger, Fritz 8   VIAFID ORCID Logo  ; Bolis, Marco 9 ; Jean‐Philippe Theurillat 9 ; Wiebringhaus, Robert 6 ; Weiss, Theresa 1 ; Haitel, Andrea 6   VIAFID ORCID Logo  ; Brehme, Marc 10   VIAFID ORCID Logo  ; Wadsak, Wolfgang 11   VIAFID ORCID Logo  ; Griss, Johannes 12   VIAFID ORCID Logo  ; Mohr, Thomas 13 ; Hofer, Alexandra 14 ; Jäger, Anton 6 ; Pollheimer, Jürgen 5   VIAFID ORCID Logo  ; Egger, Gerda 15 ; Koellensperger, Gunda 16   VIAFID ORCID Logo  ; Mann, Matthias 2   VIAFID ORCID Logo  ; Hantusch, Brigitte 6 ; Kenner, Lukas 17   VIAFID ORCID Logo 

1  Department of Pathology, Medical University of Vienna, Vienna, Austria; CBmed‐Center for Biomarker Research in Medicine GmbH, Graz, Austria 
2  Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany 
3  Department of Analytical Chemistry, University of Vienna, Vienna, Austria; Institute of Inorganic Chemistry, University of Vienna, Vienna, Austria 
4  Patho im Zentrum, St.Pölten, Austria 
5  Department of Obstetrics and Gynaecology, Medical University of Vienna, Vienna, Austria 
6  Department of Pathology, Medical University of Vienna, Vienna, Austria 
7  Unit of Pathology of Laboratory Animals, University of Veterinary Medicine Vienna, Vienna, Austria 
8  Department of Biosciences, University of Salzburg, Salzburg, Austria 
9  Institute of Oncology Research (IOR), Bellinzona, Switzerland; Università delle Svizzera italiana, Lugano, Switzerland 
10  CBmed‐Center for Biomarker Research in Medicine GmbH, Graz, Austria 
11  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 
12  Department of Dermatology, Medical University of Vienna, Vienna, Austria 
13  Department of Medicine I, Medical University of Vienna, Vienna, Austria; Science Consult DI, Thomas Mohr KG, Guntramsdorf, Austria 
14  Research Area Biochemical Engineering, Institute of Chemical, Environmental and Biological Engineering, Vienna University of Technology, Vienna, Austria 
15  Department of Pathology, Medical University of Vienna, Vienna, Austria; Ludwig Boltzmann Institute Applied Diagnostics, Vienna, Austria 
16  Department of Analytical Chemistry, University of Vienna, Vienna, Austria 
17  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 
Section
Articles
Publication year
2020
Publication date
Apr 2020
Publisher
EMBO Press
e-ISSN
17444292
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.15252/msb.20199247
ProQuest document ID
2395475716
Copyright
© 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.