Ubiquitin-proteasome Pathway-linked Gene Signatures as Prognostic Indicators in Prostate Cancer.

BACKGROUND/AIM: Prostate cancer (PCa) is the most frequently diagnosed cancer in men and a leading cause of cancer-related death. While prostate-specific antigen is a widely used biomarker, its specificity is limited. This study investigated the prognostic significance of gene subsets associated with the ubiquitin-proteasome pathway in PCa.

MATERIALS AND

METHODS

We analyzed transcriptomic and clinical data of 94 early-onset (age <55) patients with prostate cancer using public dataset. Differentially expressed genes linked to the ubiquitin-proteasome system were identified across cancer progression stages. Kaplan-Meier survival analysis, Cox regression, and least absolute shrinkage and selection operator (LASSO) modeling were applied to assess their prognostic potential.

RESULTS

Differential expression of IKBKB, UBQLN3, TMUB2, UBE2S, and BRCA1 was observed at relative-early stages of pT3a and Gleason 3+4. Similarly, HERPUD1, CDC20, UHRF1, PSMD7, PIAS3, MALT1, TNF, UBD, CD3E, CD247, SOCS1, UBE2C, CARD16, ZAP70, UBA7, and UBE3C expression levels also changed at pT3b and Gleason 4+3. At metastatic stages (pT4 and Gleason ≥8) OASL expression was up-regulated, whereas that of DDB1, RPN1, UBE3B, UBE2H, PPIL2, WWP2, and CDH1 was down-regulated. In addition, higher expression of PSMD2, CDC20, NFKB1, and STIP1 or lower expression of HERPUD2, NEDD4, ANAPC16, LNX1, and HERPUD1 was associated with poor prognoses according to the Kaplan-Meier or receiver operating characteristic analyses for biochemical recurrence-free survival. A LASSO-Cox model identified six gene candidates including LNX1, PSMD2, SUMO4, UBE2C, UBR5, and UHRF1.

CONCLUSION

The identified gene subset provides novel prognostic insights into PCa progression and survival. These findings highlight potential biomarkers and therapeutic targets within the ubiquitin-proteasome pathway, offering new avenues for personalized treatment strategies.