Opposing prognostic relevance of junction plakoglobin in distinct prostate cancer patient subsets
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Opposing prognostic relevance of junction plakoglobin in distinct prostate cancer patient subsets. / Spethmann, Tanja; Böckelmann, Lukas Clemens; Labitzky, Vera; Ahlers, Ann-Kristin; Schröder-Schwarz, Jennifer; Bonk, Sarah; Simon, Ronald; Sauter, Guido; Huland, Hartwig; Kypta, Robert; Schumacher, Udo; Lange, Tobias.
in: MOL ONCOL, Jahrgang 15, Nr. 7, 07.2021, S. 1956-1969.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Opposing prognostic relevance of junction plakoglobin in distinct prostate cancer patient subsets
AU - Spethmann, Tanja
AU - Böckelmann, Lukas Clemens
AU - Labitzky, Vera
AU - Ahlers, Ann-Kristin
AU - Schröder-Schwarz, Jennifer
AU - Bonk, Sarah
AU - Simon, Ronald
AU - Sauter, Guido
AU - Huland, Hartwig
AU - Kypta, Robert
AU - Schumacher, Udo
AU - Lange, Tobias
N1 - © 2021 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
PY - 2021/7
Y1 - 2021/7
N2 - 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.
AB - 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.
U2 - 10.1002/1878-0261.12922
DO - 10.1002/1878-0261.12922
M3 - SCORING: Journal article
C2 - 33533127
VL - 15
SP - 1956
EP - 1969
JO - MOL ONCOL
JF - MOL ONCOL
SN - 1574-7891
IS - 7
ER -