STAT3‐dependent analysis reveals PDK4 as independent predictor of recurrence in prostate cancer
Abstract Prostate cancer (PCa) has a broad spectrum of clinical behavior; hence, biomarkers are urgently needed for risk stratification. Here, we aim to find potential biomarkers for risk stratification, by utilizing a gene co‐expression network of transcriptomics data in addition to laser‐microdiss...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2020-04-01
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| Series: | Molecular Systems Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/msb.20199247 |
| _version_ | 1797284000655474688 |
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| author | Monika Oberhuber Matteo Pecoraro Mate Rusz Georg Oberhuber Maritta Wieselberg Peter Haslinger Elisabeth Gurnhofer Michaela Schlederer Tanja Limberger Sabine Lagger Jan Pencik Petra Kodajova Sandra Högler Georg Stockmaier Sandra Grund‐Gröschke Fritz Aberger Marco Bolis Jean‐Philippe Theurillat Robert Wiebringhaus Theresa Weiss Andrea Haitel Marc Brehme Wolfgang Wadsak Johannes Griss Thomas Mohr Alexandra Hofer Anton Jäger Jürgen Pollheimer Gerda Egger Gunda Koellensperger Matthias Mann Brigitte Hantusch Lukas Kenner |
| author_facet | Monika Oberhuber Matteo Pecoraro Mate Rusz Georg Oberhuber Maritta Wieselberg Peter Haslinger Elisabeth Gurnhofer Michaela Schlederer Tanja Limberger Sabine Lagger Jan Pencik Petra Kodajova Sandra Högler Georg Stockmaier Sandra Grund‐Gröschke Fritz Aberger Marco Bolis Jean‐Philippe Theurillat Robert Wiebringhaus Theresa Weiss Andrea Haitel Marc Brehme Wolfgang Wadsak Johannes Griss Thomas Mohr Alexandra Hofer Anton Jäger Jürgen Pollheimer Gerda Egger Gunda Koellensperger Matthias Mann Brigitte Hantusch Lukas Kenner |
| author_sort | Monika Oberhuber |
| collection | DOAJ |
| description | Abstract Prostate cancer (PCa) has a broad spectrum of clinical behavior; hence, biomarkers are urgently needed for risk stratification. Here, we aim to find potential biomarkers for risk stratification, by utilizing a gene co‐expression network of transcriptomics data in addition to laser‐microdissected proteomics from human and murine prostate FFPE samples. We show up‐regulation of oxidative phosphorylation (OXPHOS) in PCa on the transcriptomic level and up‐regulation of the TCA cycle/OXPHOS on the proteomic level, which is inversely correlated to STAT3 expression. We hereby identify gene expression of pyruvate dehydrogenase kinase 4 (PDK4), a key regulator of the TCA cycle, as a promising independent prognostic marker in PCa. PDK4 predicts disease recurrence independent of diagnostic risk factors such as grading, staging, and PSA level. Therefore, low PDK4 is a promising marker for PCa with dismal prognosis. |
| first_indexed | 2024-03-07T17:38:45Z |
| format | Article |
| id | doaj.art-2a34435eaf574feab86239c627dd739f |
| institution | Directory Open Access Journal |
| issn | 1744-4292 |
| language | English |
| last_indexed | 2024-03-07T17:38:45Z |
| publishDate | 2020-04-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj.art-2a34435eaf574feab86239c627dd739f2024-03-02T16:05:10ZengSpringer NatureMolecular Systems Biology1744-42922020-04-01164n/an/a10.15252/msb.20199247STAT3‐dependent analysis reveals PDK4 as independent predictor of recurrence in prostate cancerMonika Oberhuber0Matteo Pecoraro1Mate Rusz2Georg Oberhuber3Maritta Wieselberg4Peter Haslinger5Elisabeth Gurnhofer6Michaela Schlederer7Tanja Limberger8Sabine Lagger9Jan Pencik10Petra Kodajova11Sandra Högler12Georg Stockmaier13Sandra Grund‐Gröschke14Fritz Aberger15Marco Bolis16Jean‐Philippe Theurillat17Robert Wiebringhaus18Theresa Weiss19Andrea Haitel20Marc Brehme21Wolfgang Wadsak22Johannes Griss23Thomas Mohr24Alexandra Hofer25Anton Jäger26Jürgen Pollheimer27Gerda Egger28Gunda Koellensperger29Matthias Mann30Brigitte Hantusch31Lukas Kenner32Department of Pathology Medical University of Vienna Vienna AustriaDepartment of Proteomics and Signal Transduction Max Planck Institute of Biochemistry Martinsried GermanyDepartment of Analytical Chemistry University of Vienna Vienna AustriaPatho im Zentrum St.Pölten AustriaDepartment of Pathology Medical University of Vienna Vienna AustriaDepartment of Obstetrics and Gynaecology Medical University of Vienna Vienna AustriaDepartment of Pathology Medical University of Vienna Vienna AustriaDepartment of Pathology Medical University of Vienna Vienna AustriaDepartment of Pathology Medical University of Vienna Vienna AustriaUnit of Pathology of Laboratory Animals University of Veterinary Medicine Vienna Vienna AustriaDepartment of Pathology Medical University of Vienna Vienna AustriaUnit of Pathology of Laboratory Animals University of Veterinary Medicine Vienna Vienna AustriaUnit of Pathology of Laboratory Animals University of Veterinary Medicine Vienna Vienna AustriaDepartment of Biosciences University of Salzburg Salzburg AustriaDepartment of Biosciences University of Salzburg Salzburg AustriaDepartment of Biosciences University of Salzburg Salzburg AustriaInstitute of Oncology Research (IOR) Bellinzona SwitzerlandInstitute of Oncology Research (IOR) Bellinzona SwitzerlandDepartment of Pathology Medical University of Vienna Vienna AustriaDepartment of Pathology Medical University of Vienna Vienna AustriaDepartment of Pathology Medical University of Vienna Vienna AustriaCBmed‐Center for Biomarker Research in Medicine GmbH Graz AustriaCBmed‐Center for Biomarker Research in Medicine GmbH Graz AustriaDepartment of Dermatology Medical University of Vienna Vienna AustriaDepartment of Medicine I Medical University of Vienna Vienna AustriaResearch Area Biochemical Engineering Institute of Chemical Environmental and Biological Engineering Vienna University of Technology Vienna AustriaDepartment of Pathology Medical University of Vienna Vienna AustriaDepartment of Obstetrics and Gynaecology Medical University of Vienna Vienna AustriaDepartment of Pathology Medical University of Vienna Vienna AustriaDepartment of Analytical Chemistry University of Vienna Vienna AustriaDepartment of Proteomics and Signal Transduction Max Planck Institute of Biochemistry Martinsried GermanyDepartment of Pathology Medical University of Vienna Vienna AustriaDepartment of Pathology Medical University of Vienna Vienna AustriaAbstract Prostate cancer (PCa) has a broad spectrum of clinical behavior; hence, biomarkers are urgently needed for risk stratification. Here, we aim to find potential biomarkers for risk stratification, by utilizing a gene co‐expression network of transcriptomics data in addition to laser‐microdissected proteomics from human and murine prostate FFPE samples. We show up‐regulation of oxidative phosphorylation (OXPHOS) in PCa on the transcriptomic level and up‐regulation of the TCA cycle/OXPHOS on the proteomic level, which is inversely correlated to STAT3 expression. We hereby identify gene expression of pyruvate dehydrogenase kinase 4 (PDK4), a key regulator of the TCA cycle, as a promising independent prognostic marker in PCa. PDK4 predicts disease recurrence independent of diagnostic risk factors such as grading, staging, and PSA level. Therefore, low PDK4 is a promising marker for PCa with dismal prognosis.https://doi.org/10.15252/msb.20199247OXPHOSPDK4prostate cancerSTAT3TCA cycle |
| spellingShingle | Monika Oberhuber Matteo Pecoraro Mate Rusz Georg Oberhuber Maritta Wieselberg Peter Haslinger Elisabeth Gurnhofer Michaela Schlederer Tanja Limberger Sabine Lagger Jan Pencik Petra Kodajova Sandra Högler Georg Stockmaier Sandra Grund‐Gröschke Fritz Aberger Marco Bolis Jean‐Philippe Theurillat Robert Wiebringhaus Theresa Weiss Andrea Haitel Marc Brehme Wolfgang Wadsak Johannes Griss Thomas Mohr Alexandra Hofer Anton Jäger Jürgen Pollheimer Gerda Egger Gunda Koellensperger Matthias Mann Brigitte Hantusch Lukas Kenner STAT3‐dependent analysis reveals PDK4 as independent predictor of recurrence in prostate cancer Molecular Systems Biology OXPHOS PDK4 prostate cancer STAT3 TCA cycle |
| title | STAT3‐dependent analysis reveals PDK4 as independent predictor of recurrence in prostate cancer |
| title_full | STAT3‐dependent analysis reveals PDK4 as independent predictor of recurrence in prostate cancer |
| title_fullStr | STAT3‐dependent analysis reveals PDK4 as independent predictor of recurrence in prostate cancer |
| title_full_unstemmed | STAT3‐dependent analysis reveals PDK4 as independent predictor of recurrence in prostate cancer |
| title_short | STAT3‐dependent analysis reveals PDK4 as independent predictor of recurrence in prostate cancer |
| title_sort | stat3 dependent analysis reveals pdk4 as independent predictor of recurrence in prostate cancer |
| topic | OXPHOS PDK4 prostate cancer STAT3 TCA cycle |
| url | https://doi.org/10.15252/msb.20199247 |
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