{"doi":"10.21873/anticanres.17562","title":"Ubiquitin-proteasome Pathway-linked Gene Signatures as Prognostic Indicators in Prostate Cancer","abstract":"<h3>Background/Aim:</h3> 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. <h3>Materials and Methods:</h3> We analyzed transcriptomic and clinical data of 94 early-onset (age &lt;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. <h3>Results:</h3> Differential expression of <i>IKBKB, UBQLN3, TMUB2, UBE2S</i>, and <i>BRCA1</i> was observed at relative-early stages of pT3a and Gleason 3+4. Similarly, <i>HERPUD1, CDC20, UHRF1, PSMD7, PIAS3, MALT1, TNF, UBD, CD3E, CD247, SOCS1, UBE2C, CARD16, ZAP70, UBA7</i>, and <i>UBE3C</i> expression levels also changed at pT3b and Gleason 4+3. At metastatic stages (pT4 and Gleason ≥8) <i>OASL</i> expression was up-regulated, whereas that of <i>DDB1, RPN1, UBE3B, UBE2H, PPIL2, WWP2</i>, and <i>CDH1</i> was down-regulated. In addition, higher expression of <i>PSMD2, CDC20, NFKB1</i>, and <i>STIP1</i> or lower expression of <i>HERPUD2, NEDD4, ANAPC16, LNX1</i>, and <i>HERPUD1</i> 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 <i>LNX1, PSMD2, SUMO4, UBE2C, UBR5</i>, and <i>UHRF1</i>. <h3>Conclusion:</h3> 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.","journal":"Anticancer Research","year":2025,"id":543968,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9436,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1434262,"name":"Kengo Yoshii","orcid":null,"position":1,"is_corresponding":false},{"id":1434263,"name":"Masami Tanaka","orcid":null,"position":2,"is_corresponding":false},{"id":1434264,"name":"Kei Tashiro","orcid":null,"position":3,"is_corresponding":false},{"id":1433882,"name":"Yasuo Takashima","orcid":"0000-0001-8876-6673","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:53:08.338070Z","pmid":"40295064","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}