Upregulation of mitochondrial function is associated with advanced prostate cancer
1 Abstract: Background: The mitochondrial metabolism in prostate cancer (PCa) is of great importance due the unique metabolic shift from glycolysis to oxidative phosphorylation. In this study, we aimed to analyze the expression level of mitochondrial markers TOM20, DRP1 and OPA1 in benign and malig...
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| Format: | Article |
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Elsevier
2025-03-01
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| Series: | Advances in Cancer Biology - Metastasis |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667394024000182 |
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| author | Valentin Baumgartner Thomas Paul Scherer Ashkan Mortezavi Niels Rupp Holger Moch Peter Wild Susanne Dettwiler Miriam Wanner Dominik Enderlin Souzan Salemi Daniel Eberli |
| author_facet | Valentin Baumgartner Thomas Paul Scherer Ashkan Mortezavi Niels Rupp Holger Moch Peter Wild Susanne Dettwiler Miriam Wanner Dominik Enderlin Souzan Salemi Daniel Eberli |
| author_sort | Valentin Baumgartner |
| collection | DOAJ |
| description | 1 Abstract: Background: The mitochondrial metabolism in prostate cancer (PCa) is of great importance due the unique metabolic shift from glycolysis to oxidative phosphorylation. In this study, we aimed to analyze the expression level of mitochondrial markers TOM20, DRP1 and OPA1 in benign and malignant tissue, to assess if these markers are associated with different grade and stage of PCa. Materials and methods: This study assessed TOM20, DRP1, and OPA1 expression in formalin-fixed, paraffin-embedded prostate tissue samples, including benign and malignant tissue specimen. Immunohistochemistry on tissue microarrays was conducted, with staining intensities scored semi-quantitatively. Statistical analyses evaluated associations with PCa grade and stage. A survival analysis for biochemical recurrence (RFS), overall survival (OS) and disease specific survival (DSS) was performed using multivariate Cox regression analysis to assess prognostic properties of the markers. Results: In total, 527 patients were included in our analysis, which composed of 45 (8.5 %) benign prostate hyperplasia (BPH) and 482 (91.5 %) PCa samples (436 localized (90.5 %) and 46 (9.5 %) metastatic). Immunoreactivity for TOM20, DRP1 and OPA1 was strong in 2 of 43 (4.7 %), 1 of 43 (2.3 %) and 0 of 43 (0 %) of BPH control tissue. Strong marker expression was significantly increased in radical prostatectomy specimen (TOM20: 111/371 (29.9 %), DRP1: 89/373 (23.9 %), OPA1: 60/371 (16.2 %), p < 0.001) and in metastatic tissue (TOM20: 22/42 (52.4 %), DRP1: 14/42 (33.3 %), OPA1: 21/41 (51.2 %), p < 0.001). None of the markers demonstrated prognostic properties for RFS, OS, and DSS. Conclusion: A strong association between the expression of the mitochondrial markers TOM20, DRP1 and OPA1 and PCa aggressiveness was demonstrated. However, these markers were not found to be prognostic regarding RFS, OS and DSS. Future studies are needed focusing on the underlying mechanisms of the upregulation of mitochondrial metabolism in aggressive PCa and evaluate potential therapeutic implications. |
| format | Article |
| id | doaj-art-4b2af385258a4795a89cf42dc68c19aa |
| institution | DOAJ |
| issn | 2667-3940 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Advances in Cancer Biology - Metastasis |
| spelling | doaj-art-4b2af385258a4795a89cf42dc68c19aa2025-08-20T02:52:31ZengElsevierAdvances in Cancer Biology - Metastasis2667-39402025-03-011310013110.1016/j.adcanc.2024.100131Upregulation of mitochondrial function is associated with advanced prostate cancerValentin Baumgartner0Thomas Paul Scherer1Ashkan Mortezavi2Niels Rupp3Holger Moch4Peter Wild5Susanne Dettwiler6Miriam Wanner7Dominik Enderlin8Souzan Salemi9Daniel Eberli10Laboratory for Urologic Oncology and Stem Cell Therapy, Department of Urology, University Hospital Zurich, Wagistrasse 21, 8952 Schlieren, SwitzerlandLaboratory for Urologic Oncology and Stem Cell Therapy, Department of Urology, University Hospital Zurich, Wagistrasse 21, 8952 Schlieren, SwitzerlandLaboratory for Urologic Oncology and Stem Cell Therapy, Department of Urology, University Hospital Zurich, Wagistrasse 21, 8952 Schlieren, SwitzerlandDepartment of Pathology and Molecular Pathology, University Hospital Zurich, Schmelzbergstrasse 12, 8091 Zurich, Switzerland; Faculty of Medicine, University of Zurich, Zurich, SwitzerlandDepartment of Pathology and Molecular Pathology, University Hospital Zurich, Schmelzbergstrasse 12, 8091 Zurich, Switzerland; Faculty of Medicine, University of Zurich, Zurich, SwitzerlandDr. Senckenberg Institute for Pathology, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, GermanyDepartment of Pathology and Molecular Pathology, University Hospital Zurich, Schmelzbergstrasse 12, 8091 Zurich, SwitzerlandDepartment of Pathology and Molecular Pathology, University Hospital Zurich, Schmelzbergstrasse 12, 8091 Zurich, SwitzerlandLaboratory for Urologic Oncology and Stem Cell Therapy, Department of Urology, University Hospital Zurich, Wagistrasse 21, 8952 Schlieren, SwitzerlandLaboratory for Urologic Oncology and Stem Cell Therapy, Department of Urology, University Hospital Zurich, Wagistrasse 21, 8952 Schlieren, Switzerland; Corresponding author. University Hospital Zurich, Department of Urology, Laboratory for Urologic Oncology and Stem Cell Therapy, Wagistrasse 21, 4.OG, 8952 Schlieren, Switzerland.Laboratory for Urologic Oncology and Stem Cell Therapy, Department of Urology, University Hospital Zurich, Wagistrasse 21, 8952 Schlieren, Switzerland1 Abstract: Background: The mitochondrial metabolism in prostate cancer (PCa) is of great importance due the unique metabolic shift from glycolysis to oxidative phosphorylation. In this study, we aimed to analyze the expression level of mitochondrial markers TOM20, DRP1 and OPA1 in benign and malignant tissue, to assess if these markers are associated with different grade and stage of PCa. Materials and methods: This study assessed TOM20, DRP1, and OPA1 expression in formalin-fixed, paraffin-embedded prostate tissue samples, including benign and malignant tissue specimen. Immunohistochemistry on tissue microarrays was conducted, with staining intensities scored semi-quantitatively. Statistical analyses evaluated associations with PCa grade and stage. A survival analysis for biochemical recurrence (RFS), overall survival (OS) and disease specific survival (DSS) was performed using multivariate Cox regression analysis to assess prognostic properties of the markers. Results: In total, 527 patients were included in our analysis, which composed of 45 (8.5 %) benign prostate hyperplasia (BPH) and 482 (91.5 %) PCa samples (436 localized (90.5 %) and 46 (9.5 %) metastatic). Immunoreactivity for TOM20, DRP1 and OPA1 was strong in 2 of 43 (4.7 %), 1 of 43 (2.3 %) and 0 of 43 (0 %) of BPH control tissue. Strong marker expression was significantly increased in radical prostatectomy specimen (TOM20: 111/371 (29.9 %), DRP1: 89/373 (23.9 %), OPA1: 60/371 (16.2 %), p < 0.001) and in metastatic tissue (TOM20: 22/42 (52.4 %), DRP1: 14/42 (33.3 %), OPA1: 21/41 (51.2 %), p < 0.001). None of the markers demonstrated prognostic properties for RFS, OS, and DSS. Conclusion: A strong association between the expression of the mitochondrial markers TOM20, DRP1 and OPA1 and PCa aggressiveness was demonstrated. However, these markers were not found to be prognostic regarding RFS, OS and DSS. Future studies are needed focusing on the underlying mechanisms of the upregulation of mitochondrial metabolism in aggressive PCa and evaluate potential therapeutic implications.http://www.sciencedirect.com/science/article/pii/S2667394024000182Prostate cancerMitochondriaTissue microarrayGleason |
| spellingShingle | Valentin Baumgartner Thomas Paul Scherer Ashkan Mortezavi Niels Rupp Holger Moch Peter Wild Susanne Dettwiler Miriam Wanner Dominik Enderlin Souzan Salemi Daniel Eberli Upregulation of mitochondrial function is associated with advanced prostate cancer Advances in Cancer Biology - Metastasis Prostate cancer Mitochondria Tissue microarray Gleason |
| title | Upregulation of mitochondrial function is associated with advanced prostate cancer |
| title_full | Upregulation of mitochondrial function is associated with advanced prostate cancer |
| title_fullStr | Upregulation of mitochondrial function is associated with advanced prostate cancer |
| title_full_unstemmed | Upregulation of mitochondrial function is associated with advanced prostate cancer |
| title_short | Upregulation of mitochondrial function is associated with advanced prostate cancer |
| title_sort | upregulation of mitochondrial function is associated with advanced prostate cancer |
| topic | Prostate cancer Mitochondria Tissue microarray Gleason |
| url | http://www.sciencedirect.com/science/article/pii/S2667394024000182 |
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