Opposing prognostic relevance of junction plakoglobin in distinct prostate cancer patient subsets. Issue 7 (17th February 2021)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Molecular oncology. Volume 15:Issue 7(2021)
• Page Start: 1956
• Page End: 1969
• Publication Date: 2021-02-17
• Subjects: cell adhesion -- CHD1 -- ERG -- junction plakoglobin -- prostate cancer -- WNT signaling; Cancer -- Molecular aspects -- Periodicals; 616.994005
• DOI: 10.1002/1878-0261.12922
• Languages: English
• ISSNs: 1574-7891

Abstract

Abstract : 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. Abstract : Junction plakoglobin (JUP) is a component of desmosomes and adherens junctions and reported to play divergent roles in tumorigenesis. JUP expression was analyzed in prostate cancer in a large‐enough patient cohort to reflect the molecular heterogeneity of the disease. Overall, high JUP expression was associated with adverse tumor features, while low JUP expression indicated poor prognosis in CHD1 ‐deleted patients.