Opposing prognostic relevance of junction plakoglobin in distinct prostate cancer patient subsets

Abstract

Both oncogenic and tumor suppressor functions have been described for junction plakoglobin (JUP), also known as c-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.

Biomarkers Found in the Tumor Interstitial Fluid may Help Explain the Differential Behavior Among Keratinocyte Carcinomas

“…Another difference was that SCC samples were enriched in cytoskeleton proteins, while BCC samples were not. Most of these cytoskeleton proteins have been previously described as present in the exosomes of diverse tumors (ExoCarta) ( 31 ) and have been related to poor prognoses such as LAD1, SFN, and JUP ( 32 , 33 , 34 , 35 ). Then, we propound that the differences between SCC and BCC-TIF composition could explain SCC aggressiveness and metastatic output.…”

Hsa-miR-133a-3p, miR-1-3p, GOLPH3 and JUP combination results in a good biomarker to distinguish between prostate cancer and non-prostate cancer patients

“…Spethmann et al., demonstrated that the opposing biological roles of JUP were reflected by antagonistic prognostic effects in different molecular subtypes. High expression of JUP was associated with adverse tumor stage, high Gleason grade lymph node metastases in a subset of PCa patients without TMPRSS2:ERG fusion ( 46 ). Also, Overexpression of JUP was linked to strong androgen receptor expression, high cell proliferation, and PTEN and FOXP1 deletion ( 46 ).…”

“…High expression of JUP was associated with adverse tumor stage, high Gleason grade lymph node metastases in a subset of PCa patients without TMPRSS2:ERG fusion ( 46 ). Also, Overexpression of JUP was linked to strong androgen receptor expression, high cell proliferation, and PTEN and FOXP1 deletion ( 46 ). On the other hand, it was found that SOX4 interacts with JUP in a Wnt-dependent manner in LNCaP cells and this complex may inhibit Wnt signaling ( 47 ).…”

Comparative Genomic Hybridization and Transcriptome Sequencing Reveal Genes with Gain in Acute Lymphoblastic Leukemia: JUP Expression Emerges as a Survival-Related Gene

“…In addition, γ- and β-catenin were essential for maintaining leukemic stem cells in AML [ 72 ], while γ-catenin has also been found to be overexpressed in ovarian [ 73 ] and gastric cancer [ 74 ]. JUP expression in prostate cancer is controversial since changes depending on the stage [ 75 ]. In our study, JUP was found to be highly expressed in the SUP-B15 cell line and B-ALL individuals ( Figure 5 and Figure 6 A, respectively); moreover, its high expression yielded a significant correlation with worse overall survival in B-ALL ( Figure 8 ).…”