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. 2023 Jul 29;14(8):1558.
doi: 10.3390/genes14081558.

WSB1 Involvement in Prostate Cancer Progression

Laura Boldrini  1 , Massimo Bardi  2
Affiliations

WSB1 Involvement in Prostate Cancer Progression

Laura Boldrini et al. Genes (Basel). .

Abstract

Prostate cancer (PC) is polygenic disease involving many genes, and more importantly a host of gene-gene interactions, including transcriptional factors. The WSB1 gene is a transcriptional target of numerous oncoproteins, and its dysregulation can contribute to tumor progression by abnormal activation of targeted oncogenes. Using data from the Cancer Genome Atlas, we tested the possible involvement of WSB1 in PC progression. A multi-dimensional scaling (MDS) model was applied to clarify the association of WSB1 expression with other key genes, such as c-myc, ERG, Enhancer of Zeste 1 and 2 (EHZ1 and EZH2), WNT10a, and WNT 10b. An increased WSB1 expression was associated with higher PC grades and with a worse prognosis. It was also positively related to EZH1, EZH2, WNT10a, and WNT10b. Moreover, MDS showed the central role of WSB1 in influencing the other target genes by its central location on the map. Our study is the first to show a link between WSB1 expression and other genes involved in PC progression, suggesting a novel role for WSB1 in PC progression. This network between WSB1 and EZH2 through WNT/β-catenin may have an important role in PC progression, as suggested by the association between high WSB1 expression and unfavorable prognosis in our analysis.

Keywords: MDS; WSB1; prostate cancer; survival.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Differences in DFI among grading groups by the ISUP consensus recommendations. Low group included grade 1, 2, and 3 by ISUP (1 for GS ≤ 6; 2 for GS 7, 3 + 4; 3 for GS 7, 4 + 3); high group included grade 4, and 5 by ISUP (4 for GS 8, 4 + 4, 3 + 5, 5 + 3; 5 for GS 9 and 10, 4 + 5, 5 + 4, 5 + 5). * High grade PC showed a higher probability to have a shorter DFI, with a significant p-value (p = 0.05).
Figure 2
Figure 2
Map of the association among the variables included in the multidimensional scaling (MDS) model: the central role of WSB1 in influencing the other target genes was demonstrated by its central location on the map.
Figure 3
Figure 3
Kaplan–Meier curves showed a shorter DFI and OS in patients with high WSB1 expression in comparison with patients with low WSB1 levels (Generalized Wilcoxon χ2 = 13.280, p < 0.001 and χ2 = 6.196, p = 0.013, respectively).
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