Open AccessOpposing prognostic relevance of junction plakoglobin in distinct prostate cancer patient subsets
Author(s) -
Spethmann Tanja,
Böckelmann Lukas Clemens,
Labitzky Vera,
Ahlers AnnKristin,
SchröderSchwarz Jennifer,
Bonk Sarah,
Simon Ronald,
Sauter Guido,
Huland Hartwig,
Kypta Robert,
Schumacher Udo,
Lange Tobias
Publication year - 2021
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.12922
Subject(s) - prostate cancer , cancer research , pten , biochemical recurrence , biology , tissue microarray , claudin , prostatectomy , tmprss2 , prostate , cancer , medicine , apoptosis , genetics , tight junction , disease , pi3k/akt/mtor pathway , covid-19 , infectious disease (medical specialty)
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.