Opposing prognostic relevance of junction plakoglobin in distinct prostate cancer patient subsets
Both oncogenic and tumor suppressor functions have been described for junction plakoglobin (JUP), also known as γ‐catenin. To clarify the role of JUP in prostate cancer, JUP protein expression was immunohistochemically detected in a tissue microarray containing 11 267 individual prostatectomy specim...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-07-01
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| Series: | Molecular Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/1878-0261.12922 |
| _version_ | 1818656109350617088 |
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| author | Tanja Spethmann Lukas Clemens Böckelmann Vera Labitzky Ann‐Kristin Ahlers Jennifer Schröder‐Schwarz Sarah Bonk Ronald Simon Guido Sauter Hartwig Huland Robert Kypta Udo Schumacher Tobias Lange |
| author_facet | Tanja Spethmann Lukas Clemens Böckelmann Vera Labitzky Ann‐Kristin Ahlers Jennifer Schröder‐Schwarz Sarah Bonk Ronald Simon Guido Sauter Hartwig Huland Robert Kypta Udo Schumacher Tobias Lange |
| author_sort | Tanja Spethmann |
| collection | DOAJ |
| description | Both oncogenic and tumor suppressor functions have been described for junction plakoglobin (JUP), also known as γ‐catenin. To clarify the role of JUP in prostate cancer, JUP protein expression was immunohistochemically detected in a tissue microarray containing 11 267 individual prostatectomy specimens. Considering all patients, high JUP expression was associated with adverse tumor stage (P = 0.0002), high Gleason grade (P < 0.0001), and lymph node metastases (P = 0.011). These associations were driven mainly by the subset without TMPRSS2:ERG fusion, in which high JUP expression was an independent predictor of poor prognosis (multivariate analyses, P = 0.0054) and early biochemical recurrence (P = 0.0003). High JUP expression was further linked to strong androgen receptor expression (P < 0.0001), high cell proliferation, and PTEN and FOXP1 deletion (P < 0.0001). In the ERG‐negative subset, high JUP expression was additionally linked to MAP3K7 (P = 0.0007) and CHD1 deletion (P = 0.0021). Contrasting the overall prognostic effect of JUP, low JUP expression indicated poor prognosis in the fraction of CHD1‐deleted patients (P = 0.039). In this subset, the association of high JUP and high cell proliferation was specifically absent. In conclusion, the controversial biological roles of JUP are reflected by antagonistic prognostic effects in distinct prostate cancer patient subsets. |
| first_indexed | 2024-12-17T03:20:21Z |
| format | Article |
| id | doaj.art-7121450caf7b4f2591affd5fcf9ae787 |
| institution | Directory Open Access Journal |
| issn | 1574-7891 1878-0261 |
| language | English |
| last_indexed | 2024-12-17T03:20:21Z |
| publishDate | 2021-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj.art-7121450caf7b4f2591affd5fcf9ae7872022-12-21T22:05:32ZengWileyMolecular Oncology1574-78911878-02612021-07-011571956196910.1002/1878-0261.12922Opposing prognostic relevance of junction plakoglobin in distinct prostate cancer patient subsetsTanja Spethmann0Lukas Clemens Böckelmann1Vera Labitzky2Ann‐Kristin Ahlers3Jennifer Schröder‐Schwarz4Sarah Bonk5Ronald Simon6Guido Sauter7Hartwig Huland8Robert Kypta9Udo Schumacher10Tobias Lange11Institute of Anatomy and Experimental Morphology Center for Experimental Medicine University Cancer Center HamburgUniversity Medical Center Hamburg‐Eppendorf GermanyInstitute of Anatomy and Experimental Morphology Center for Experimental Medicine University Cancer Center HamburgUniversity Medical Center Hamburg‐Eppendorf GermanyInstitute of Anatomy and Experimental Morphology Center for Experimental Medicine University Cancer Center HamburgUniversity Medical Center Hamburg‐Eppendorf GermanyInstitute of Anatomy and Experimental Morphology Center for Experimental Medicine University Cancer Center HamburgUniversity Medical Center Hamburg‐Eppendorf GermanyInstitute of Anatomy and Experimental Morphology Center for Experimental Medicine University Cancer Center HamburgUniversity Medical Center Hamburg‐Eppendorf GermanyGeneral, Visceral and Thoracic Surgery Department University Medical Center Hamburg‐Eppendorf GermanyInstitute of Pathology University Medical Center Hamburg‐Eppendorf GermanyInstitute of Pathology University Medical Center Hamburg‐Eppendorf GermanyMartini‐Klinik, Prostate Cancer Center University Medical Center Hamburg‐Eppendorf GermanyDepartment of Surgery and Cancer Imperial College London UKInstitute of Anatomy and Experimental Morphology Center for Experimental Medicine University Cancer Center HamburgUniversity Medical Center Hamburg‐Eppendorf GermanyInstitute of Anatomy and Experimental Morphology Center for Experimental Medicine University Cancer Center HamburgUniversity Medical Center Hamburg‐Eppendorf GermanyBoth oncogenic and tumor suppressor functions have been described for junction plakoglobin (JUP), also known as γ‐catenin. To clarify the role of JUP in prostate cancer, JUP protein expression was immunohistochemically detected in a tissue microarray containing 11 267 individual prostatectomy specimens. Considering all patients, high JUP expression was associated with adverse tumor stage (P = 0.0002), high Gleason grade (P < 0.0001), and lymph node metastases (P = 0.011). These associations were driven mainly by the subset without TMPRSS2:ERG fusion, in which high JUP expression was an independent predictor of poor prognosis (multivariate analyses, P = 0.0054) and early biochemical recurrence (P = 0.0003). High JUP expression was further linked to strong androgen receptor expression (P < 0.0001), high cell proliferation, and PTEN and FOXP1 deletion (P < 0.0001). In the ERG‐negative subset, high JUP expression was additionally linked to MAP3K7 (P = 0.0007) and CHD1 deletion (P = 0.0021). Contrasting the overall prognostic effect of JUP, low JUP expression indicated poor prognosis in the fraction of CHD1‐deleted patients (P = 0.039). In this subset, the association of high JUP and high cell proliferation was specifically absent. In conclusion, the controversial biological roles of JUP are reflected by antagonistic prognostic effects in distinct prostate cancer patient subsets.https://doi.org/10.1002/1878-0261.12922cell adhesionCHD1ERGjunction plakoglobinprostate cancerWNT signaling |
| spellingShingle | Tanja Spethmann Lukas Clemens Böckelmann Vera Labitzky Ann‐Kristin Ahlers Jennifer Schröder‐Schwarz Sarah Bonk Ronald Simon Guido Sauter Hartwig Huland Robert Kypta Udo Schumacher Tobias Lange Opposing prognostic relevance of junction plakoglobin in distinct prostate cancer patient subsets Molecular Oncology cell adhesion CHD1 ERG junction plakoglobin prostate cancer WNT signaling |
| title | Opposing prognostic relevance of junction plakoglobin in distinct prostate cancer patient subsets |
| title_full | Opposing prognostic relevance of junction plakoglobin in distinct prostate cancer patient subsets |
| title_fullStr | Opposing prognostic relevance of junction plakoglobin in distinct prostate cancer patient subsets |
| title_full_unstemmed | Opposing prognostic relevance of junction plakoglobin in distinct prostate cancer patient subsets |
| title_short | Opposing prognostic relevance of junction plakoglobin in distinct prostate cancer patient subsets |
| title_sort | opposing prognostic relevance of junction plakoglobin in distinct prostate cancer patient subsets |
| topic | cell adhesion CHD1 ERG junction plakoglobin prostate cancer WNT signaling |
| url | https://doi.org/10.1002/1878-0261.12922 |
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