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Proteomic Analysis Identifies NDUFS1 and ATP5O as Novel Markers for Survival Outcome in Prostate Cancer

R. Wiebringhaus, M. Pecoraro, HA. Neubauer, K. Trachtová, B. Trimmel, M. Wieselberg, J. Pencik, G. Egger, C. Krall, R. Moriggl, M. Mann, B. Hantusch, L. Kenner

. 2021 ; 13 (23) : . [pub] 20211130

Language English Country Switzerland

Document type Journal Article

Grant support
FA791A0906.FFG COMET Competence Center CBmed - Center for Biomarker 326 Research in Medicine
P26011 FWF Austrian Science Fund

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.

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$a Pecoraro, Matteo $u Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland
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$a Trachtová, Karolína $u Central European Institute of Technology, Masaryk University, 60177 Brno, Czech Republic $u Christian Doppler Laboratory for Applied Metabolomics (CDL-AM), Medical University of Vienna, 1090 Vienna, Austria $u Division of Nuclear Medicine, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, 1090 Vienna, Austria
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