We aimed to identify novel markers for aggressive prostate cancer in a STAT3-low proteomics-derived dataset of mitochondrial proteins by immunohistochemical analysis and correlation with transcriptomic data and biochemical recurrence in a STAT3 independent PCa cohort. Formalin-fixed paraffin-embedded tissue (FFPE) sample selection for proteomic analysis and tissue-microarray (TMA) generation was conducted from a cohort of PCa patients. Retrospective data analysis was performed with the same cohort. 153 proteins differentially expressed between STAT3-low and STAT3-high samples were identified. Out of these, 46 proteins were associated with mitochondrial processes including oxidative phosphorylation (OXPHOS), and 45 proteins were upregulated, including NDUFS1/ATP5O. In a STAT3 independent PCa cohort, high expression of NDUFS1/ATP5O was confirmed by immunocytochemistry (IHC) and was significantly associated with earlier biochemical recurrence (BCR). mRNA expression levels for these two genes were significantly higher in intra-epithelial neoplasia and in PCa compared to benign prostate glands. NDUFS1/ATP5O levels are increased both at the mRNA and protein level in aggressive PCa. Our results provide evidence that NDUFS1/ATP5O could be used to identify high-risk PCa patients.

Center for Biomarker Research in Medicine 8010 Graz Austria

Central European Institute of Technology Masaryk University 60177 Brno Czech Republic

Christian Doppler Laboratory for Applied Metabolomics Medical University of Vienna 1090 Vienna Austria

Department of Otolaryngology University Hospital LMU Munich 81377 Munich Germany

Department of Pathology Medical University of Vienna 1090 Vienna Austria

Department of Proteomics and Signal Transduction Max Planck Institute of Biochemistry 82152 Martinsried Germany

Division of Nuclear Medicine Department of Biomedical Imaging and Image Guided Therapy Medical University of Vienna 1090 Vienna Austria

Institute for Research in Biomedicine Università della Svizzera Italiana 6500 Bellinzona Switzerland

Institute for Statistics Medical University of Vienna 1090 Vienna Austria

Institute of Animal Breeding and Genetics University of Veterinary Medicine Vienna 1210 Vienna Austria

Ludwig Boltzmann Institute Applied Diagnostics 1090 Vienna Austria

Unit for Laboratory Animal Pathology University of Veterinary Medicine Vienna 1210 Vienna Austria

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