{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T22:02:06Z","timestamp":1770328926266,"version":"3.49.0"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T00:00:00Z","timestamp":1748304000000},"content-version":"vor","delay-in-days":26,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32200533"],"award-info":[{"award-number":["32200533"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32270705"],"award-info":[{"award-number":["32270705"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20241796"],"award-info":[{"award-number":["BK20241796"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Suzhou Science and Technology Plan Project","award":["SLJ2022008"],"award-info":[{"award-number":["SLJ2022008"]}]},{"name":"Suzhou Applied Basic Research Technology Innovation Program","award":["SYW2024074"],"award-info":[{"award-number":["SYW2024074"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Prostate cancer (PCa) is observed with high incidence in men worldwide. Ferroptosis, occurred from disorders in a series of gene and pathway regulation, is an emerging target against cancer. However, most of the computational approaches solely treated ferroptosis-related genes (FRGs) as independent variables in model training, and the interactions among FRGs and other candidates were not fully deciphered in a disease-specific content. In this study, a novel network-based and knowledge-guided bioinformatics model was proposed by integrating ferroptosis-related prior knowledge with topological and functional characterization on a protein\u2013protein interaction network for biomarker discovery in PCa development and ferroptosis. The model started at a random walk with restart algorithm for weighting genes close to known FRGs in the PCa-specific network to extract a core subnetwork for robustness and vulnerability analysis. Then key regulatory modules and a candidate gene, i.e. PRKCA, were respectively identified using a multi-level prioritization strategy with hub-bottleneck node filtering, edge-based gene co-expression measuring, community module detecting and a newly defined Ferr.neighbor functional score. The experimental validation using human clinical samples, cell lines, and nude mice convinced the role of PRKCA as a latent biomarker and a tumor suppressor in PCa carcinogenesis with a potential mechanism on triggering GPX4-mediated ferroptosis of PCa cells. This study provides a general-purpose systems biology framework for significant FRG screening, and future translational perspectives of PRKCA as a novel diagnostic and therapeutic signature for PCa management should be explored.<\/jats:p>","DOI":"10.1093\/bib\/bbaf220","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T11:36:05Z","timestamp":1747740965000},"source":"Crossref","is-referenced-by-count":3,"title":["Knowledge-guided multi-level network modeling with experimental characterization identifies PRKCA as a novel biomarker and tumor suppressor triggering ferroptosis in prostate cancer"],"prefix":"10.1093","volume":"26","author":[{"given":"Yuxin","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Urology, the First Affiliated Hospital of Soochow University , No. 899 Pinghai Road, Gusu District, Suzhou 215000 ,","place":["China"]},{"name":"Department of Medical Systems Biology, School of Basic Medical Sciences, Suzhou Medical College of Soochow University , No. 199 Renai Road, Suzhou Industrial Park, Suzhou 215123 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zongming","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Urology, the First Affiliated Hospital of Soochow University , No. 899 Pinghai Road, Gusu District, Suzhou 215000 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jixiang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Urology, the First Affiliated Hospital of Soochow University , No. 899 Pinghai Road, Gusu District, Suzhou 215000 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hubo","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Urology, the First Affiliated Hospital of Soochow University , No. 899 Pinghai Road, Gusu District, Suzhou 215000 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Urology, the First Affiliated Hospital of Soochow University , No. 899 Pinghai Road, Gusu District, Suzhou 215000 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"He","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Urology, the First Affiliated Hospital of Soochow University , No. 899 Pinghai Road, Gusu District, Suzhou 215000 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuedong","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Urology, the First Affiliated Hospital of Soochow University , No. 899 Pinghai Road, Gusu District, Suzhou 215000 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenying","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Medical Systems Biology, School of Basic Medical Sciences, Suzhou Medical College of Soochow University , No. 199 Renai Road, Suzhou Industrial Park, Suzhou 215123 ,","place":["China"]},{"name":"Suzhou Key Lab of Multi-modal Data Fusion and Intelligent Healthcare, Computing Science and Artificial Intelligence College, Suzhou City University , No. 1188 Wuzhong Avenue, Wuzhong District, Suzhou 215004 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Qi","sequence":"additional","affiliation":[{"name":"School of Chemistry and Life Sciences, Suzhou University of Science and Technology , No. 99 Xuefu Road, Huqiu District, Suzhou 215011 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuhua","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Urology, the First Affiliated Hospital of Soochow University , No. 899 Pinghai Road, Gusu District, Suzhou 215000 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,5,20]]},"reference":[{"key":"2025052712095241500_ref1","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J Clin"},{"key":"2025052712095241500_ref2","doi-asserted-by":"publisher","first-page":"12","DOI":"10.3322\/caac.21820","article-title":"Cancer statistics, 2024","volume":"74","author":"Siegel","year":"2024","journal-title":"CA Cancer J 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