Human Prostate Cancer Is Characterized by an Increase in Urea Cycle Metabolites
Despite it being the most common incident of cancer among men, the pathophysiological mechanisms contributing to prostate cancer (PCa) are still poorly understood. Altered mitochondrial metabolism is postulated to play a role in the development of PCa. To determine the key metabolites (which include...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-07-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/7/1814 |
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| author | Andras Franko Yaping Shao Martin Heni Jörg Hennenlotter Miriam Hoene Chunxiu Hu Xinyu Liu Xinjie Zhao Qingqing Wang Andreas L. Birkenfeld Tilman Todenhöfer Arnulf Stenzl Andreas Peter Hans-Ulrich Häring Rainer Lehmann Guowang Xu Stefan Z. Lutz |
| author_facet | Andras Franko Yaping Shao Martin Heni Jörg Hennenlotter Miriam Hoene Chunxiu Hu Xinyu Liu Xinjie Zhao Qingqing Wang Andreas L. Birkenfeld Tilman Todenhöfer Arnulf Stenzl Andreas Peter Hans-Ulrich Häring Rainer Lehmann Guowang Xu Stefan Z. Lutz |
| author_sort | Andras Franko |
| collection | DOAJ |
| description | Despite it being the most common incident of cancer among men, the pathophysiological mechanisms contributing to prostate cancer (PCa) are still poorly understood. Altered mitochondrial metabolism is postulated to play a role in the development of PCa. To determine the key metabolites (which included mitochondrial oncometabolites), benign prostatic and cancer tissues of patients with PCa were analyzed using capillary electrophoresis and liquid chromatography coupled with mass spectrometry. Gene expression was studied using real-time PCR. In PCa tissues, we found reduced levels of early tricarboxylic acid cycle metabolites, whereas the contents of urea cycle metabolites including aspartate, argininosuccinate, arginine, proline, and the oncometabolite fumarate were higher than that in benign controls. Fumarate content correlated positively with the gene expression of oncogenic HIF1α and NFκB pathways, which were significantly higher in the PCa samples than in the benign controls. Furthermore, data from the TCGA database demonstrated that prostate cancer patients with activated NFκB pathway had a lower survival rate. In summary, our data showed that fumarate content was positively associated with carcinogenic genes. |
| first_indexed | 2024-03-10T18:39:15Z |
| format | Article |
| id | doaj.art-2d93dba4fbff48f88360a756cf2b7726 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T18:39:15Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-2d93dba4fbff48f88360a756cf2b77262023-11-20T06:00:06ZengMDPI AGCancers2072-66942020-07-01127181410.3390/cancers12071814Human Prostate Cancer Is Characterized by an Increase in Urea Cycle MetabolitesAndras Franko0Yaping Shao1Martin Heni2Jörg Hennenlotter3Miriam Hoene4Chunxiu Hu5Xinyu Liu6Xinjie Zhao7Qingqing Wang8Andreas L. Birkenfeld9Tilman Todenhöfer10Arnulf Stenzl11Andreas Peter12Hans-Ulrich Häring13Rainer Lehmann14Guowang Xu15Stefan Z. Lutz16Department of Internal Medicine, Division of Endocrinology, Diabetology and Nephrology, University Hospital Tübingen, 72076 Tübingen, GermanyCAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, ChinaDepartment of Internal Medicine, Division of Endocrinology, Diabetology and Nephrology, University Hospital Tübingen, 72076 Tübingen, GermanyDepartment of Urology, University Hospital Tübingen, 72076 Tübingen, GermanyInstitute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University Hospital Tübingen, 72076 Tübingen, GermanyCAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, ChinaCAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, ChinaCAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, ChinaCAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, ChinaDepartment of Internal Medicine, Division of Endocrinology, Diabetology and Nephrology, University Hospital Tübingen, 72076 Tübingen, GermanyDepartment of Urology, University Hospital Tübingen, 72076 Tübingen, GermanyDepartment of Urology, University Hospital Tübingen, 72076 Tübingen, GermanyInstitute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University Hospital Tübingen, 72076 Tübingen, GermanyDepartment of Internal Medicine, Division of Endocrinology, Diabetology and Nephrology, University Hospital Tübingen, 72076 Tübingen, GermanyInstitute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, 72076 Tübingen, GermanyCAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, ChinaDepartment of Internal Medicine, Division of Endocrinology, Diabetology and Nephrology, University Hospital Tübingen, 72076 Tübingen, GermanyDespite it being the most common incident of cancer among men, the pathophysiological mechanisms contributing to prostate cancer (PCa) are still poorly understood. Altered mitochondrial metabolism is postulated to play a role in the development of PCa. To determine the key metabolites (which included mitochondrial oncometabolites), benign prostatic and cancer tissues of patients with PCa were analyzed using capillary electrophoresis and liquid chromatography coupled with mass spectrometry. Gene expression was studied using real-time PCR. In PCa tissues, we found reduced levels of early tricarboxylic acid cycle metabolites, whereas the contents of urea cycle metabolites including aspartate, argininosuccinate, arginine, proline, and the oncometabolite fumarate were higher than that in benign controls. Fumarate content correlated positively with the gene expression of oncogenic HIF1α and NFκB pathways, which were significantly higher in the PCa samples than in the benign controls. Furthermore, data from the TCGA database demonstrated that prostate cancer patients with activated NFκB pathway had a lower survival rate. In summary, our data showed that fumarate content was positively associated with carcinogenic genes.https://www.mdpi.com/2072-6694/12/7/1814prostate cancermetabolomicsurea cyclefumarateoncometaboliteNFκB |
| spellingShingle | Andras Franko Yaping Shao Martin Heni Jörg Hennenlotter Miriam Hoene Chunxiu Hu Xinyu Liu Xinjie Zhao Qingqing Wang Andreas L. Birkenfeld Tilman Todenhöfer Arnulf Stenzl Andreas Peter Hans-Ulrich Häring Rainer Lehmann Guowang Xu Stefan Z. Lutz Human Prostate Cancer Is Characterized by an Increase in Urea Cycle Metabolites Cancers prostate cancer metabolomics urea cycle fumarate oncometabolite NFκB |
| title | Human Prostate Cancer Is Characterized by an Increase in Urea Cycle Metabolites |
| title_full | Human Prostate Cancer Is Characterized by an Increase in Urea Cycle Metabolites |
| title_fullStr | Human Prostate Cancer Is Characterized by an Increase in Urea Cycle Metabolites |
| title_full_unstemmed | Human Prostate Cancer Is Characterized by an Increase in Urea Cycle Metabolites |
| title_short | Human Prostate Cancer Is Characterized by an Increase in Urea Cycle Metabolites |
| title_sort | human prostate cancer is characterized by an increase in urea cycle metabolites |
| topic | prostate cancer metabolomics urea cycle fumarate oncometabolite NFκB |
| url | https://www.mdpi.com/2072-6694/12/7/1814 |
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