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

Wiebringhaus, Robert; Pecoraro, Matteo; Neubauer, Heidi A.; Trachtová, Karolína; Trimmel, Bettina; Wieselberg, Maritta; Pencik, Jan; Egger, Gerda; Krall, Christoph; Moriggl, Richard; Mann, Matthias; Hantusch, Brigitte; Kenner, Lukas

doi:10.3390/cancers13236036

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

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Department of Pathology, Medical University of Vienna, 1090 Vienna, Austria

Department of Otolaryngology, University Hospital, LMU Munich, 81377 Munich, Germany

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

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

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Central European Institute of Technology, Masaryk University, 60177 Brno, Czech Republic

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Christian Doppler Laboratory for Applied Metabolomics (CDL-AM), Medical University of Vienna, 1090 Vienna, Austria

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

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Ludwig Boltzmann Institute Applied Diagnostics, 1090 Vienna, Austria

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Institute for Statistics, Medical University of Vienna, 1090 Vienna, Austria

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

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Center for Biomarker Research in Medicine (CBmed), 8010 Graz, Austria

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

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These authors contributed equally.

Academic Editor: Constantin N. Baxevanis

Cancers 2021, 13(23), 6036; https://doi.org/10.3390/cancers13236036

Received: 12 October 2021 / Revised: 23 November 2021 / Accepted: 24 November 2021 / Published: 30 November 2021

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Due to the heterogeneity of prostate cancer (PCa), it is still difficult to provide risk stratification. Metabolic changes in PCa tissue have been described during tumor progression at genetic and transcriptomic level, but these have not yet clearly contributed to improved diagnosis and therapy. The aim of our study was to identify novel markers for aggressive prostate cancer in a proteomics-derived dataset by immunohistochemical analysis and correlation with transcriptomic data. Here, we provide potential new markers—NDUFS1 and ATP5O—for risk stratification in PCa. Additionally, we reveal for the first time a concordant increase of NDUFS1/ATP5O of mRNA expression in transcriptomic datasets and at protein level.

Abstract

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. View Full-Text

Keywords: prostate cancer; FFPE-proteomics; OXPHOS; NDUFS1; ATP5O; STAT3; transcriptomics

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MDPI and ACS Style

Wiebringhaus, R.; Pecoraro, M.; Neubauer, H.A.; Trachtová, K.; Trimmel, B.; Wieselberg, M.; Pencik, J.; Egger, G.; Krall, C.; Moriggl, R.; Mann, M.; Hantusch, B.; Kenner, L. Proteomic Analysis Identifies NDUFS1 and ATP5O as Novel Markers for Survival Outcome in Prostate Cancer. Cancers 2021, 13, 6036. https://doi.org/10.3390/cancers13236036

AMA Style

Wiebringhaus R, Pecoraro M, Neubauer HA, Trachtová K, Trimmel B, Wieselberg M, Pencik J, Egger G, Krall C, Moriggl R, Mann M, Hantusch B, Kenner L. Proteomic Analysis Identifies NDUFS1 and ATP5O as Novel Markers for Survival Outcome in Prostate Cancer. Cancers. 2021; 13(23):6036. https://doi.org/10.3390/cancers13236036

Chicago/Turabian Style

Wiebringhaus, Robert, Matteo Pecoraro, Heidi A. Neubauer, Karolína Trachtová, Bettina Trimmel, Maritta Wieselberg, Jan Pencik, Gerda Egger, Christoph Krall, Richard Moriggl, Matthias Mann, Brigitte Hantusch, and Lukas Kenner. 2021. "Proteomic Analysis Identifies NDUFS1 and ATP5O as Novel Markers for Survival Outcome in Prostate Cancer" Cancers 13, no. 23: 6036. https://doi.org/10.3390/cancers13236036

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

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