{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T07:13:36Z","timestamp":1777878816341,"version":"3.51.4"},"reference-count":27,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Genomic instability is a key feature of cancer and plays a central role in tumor progression. One emerging metric for genomic instability is the fraction of genome altered (FGA), which quantifies the proportion of the genome affected by copy number alterations. Previous studies in various solid tumors have shown that high FGA is associated with aggressive disease and adverse clinical outcomes. However, the clinical significance of FGA in prostate cancer (PC) remains unclear. In this study, we investigated the role of FGA as a potential biomarker of tumor aggressiveness and a poor prognosis in PC using several large\u2010scale public databases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We analyzed the processed data from previous large\u2010scale PC studies available through the cBioPortal database: MSK CHORD 2024 (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20093211), MSK 2021 (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20092069), MSK 2020 mCSPC (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009424), SU2C\/PCF mCRPC (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009444), and AACR Project GENIE (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20095306). Associations between FGA and clinical parameters such as T stage, Gleason score (GS), tumor volume, metastatic burden, pathological subtype, and treatment history were evaluated. Kaplan\u2013Meier survival analysis was used to assess the prognostic value of FGA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      High FGA was significantly associated with aggressive clinical features, including higher T stage, GS, metastatic burden, and neuroendocrine prostate cancer histology. FGA increased after most therapeutic interventions. Patients with high FGA had significantly poorer overall survival across nearly all treatment modalities. An oncoplot analysis revealed a higher frequency of somatic alterations in key driver genes, including\n                      <jats:italic>AR, PTEN<\/jats:italic>\n                      , and\n                      <jats:italic>TP53<\/jats:italic>\n                      , in high\u2010FGA tumors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>FGA was closely associated with tumor aggressiveness, therapy\u2010induced genomic instability, and a poor prognosis in PC. It may serve as a clinically relevant biomarker across diverse treatment contexts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pros.70042","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T04:44:15Z","timestamp":1756788255000},"page":"1513-1521","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Comprehensive Analysis of Fraction of Genome Altered in Prostate Cancer Treatment"],"prefix":"10.1002","volume":"85","author":[{"given":"Kazuma","family":"Yukihiro","sequence":"first","affiliation":[{"name":"Department of Urology Hiroshima University Graduate School of Biomedical Sciences Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yohei","family":"Sekino","sequence":"additional","affiliation":[{"name":"Department of Urology Hiroshima University Graduate School of Biomedical Sciences Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Go","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pathology, Department of Molecular Biosciences Radiation Effects Research Foundation Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1953-3240","authenticated-orcid":false,"given":"Tomoya","family":"Hatayama","sequence":"additional","affiliation":[{"name":"Department of Urology Hiroshima University Graduate School of Biomedical Sciences Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4981-0074","authenticated-orcid":false,"given":"Hiroyuki","family":"Shikuma","sequence":"additional","affiliation":[{"name":"Department of Urology Hiroshima University Graduate School of Biomedical Sciences Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryo","family":"Tasaka","sequence":"additional","affiliation":[{"name":"Department of Urology Hiroshima University Graduate School of Biomedical Sciences Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuki","family":"Kohada","sequence":"additional","affiliation":[{"name":"Department of Urology Hiroshima University Graduate School of Biomedical Sciences Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9077-4733","authenticated-orcid":false,"given":"Kenshiro","family":"Takemoto","sequence":"additional","affiliation":[{"name":"Department of Urology Hiroshima University Graduate School of Biomedical Sciences Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3485-0751","authenticated-orcid":false,"given":"Miki","family":"Naito","sequence":"additional","affiliation":[{"name":"Department of Urology Hiroshima University Graduate School of Biomedical Sciences Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8397-115X","authenticated-orcid":false,"given":"Shunsuke","family":"Miyamoto","sequence":"additional","affiliation":[{"name":"Department of Urology Hiroshima University Graduate School of Biomedical Sciences Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2098-3916","authenticated-orcid":false,"given":"Kohei","family":"Kobatake","sequence":"additional","affiliation":[{"name":"Department of Urology Hiroshima University Graduate School of Biomedical Sciences Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2223-2403","authenticated-orcid":false,"given":"Hiroyuki","family":"Kitano","sequence":"additional","affiliation":[{"name":"Department of Urology Hiroshima University Graduate School of Biomedical Sciences Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keisuke","family":"Goto","sequence":"additional","affiliation":[{"name":"Department of Urology Hiroshima University Graduate School of Biomedical Sciences Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akihiro","family":"Goriki","sequence":"additional","affiliation":[{"name":"Department of Urology Hiroshima University Graduate School of Biomedical Sciences Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keisuke","family":"Hieda","sequence":"additional","affiliation":[{"name":"Department of Urology Hiroshima University Graduate School of Biomedical Sciences Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7014-6812","authenticated-orcid":false,"given":"Nobuyuki","family":"Hinata","sequence":"additional","affiliation":[{"name":"Department of Urology Hiroshima University Graduate School of Biomedical Sciences Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,9]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15205047"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11912-020-01003-9"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.cd-11-0130"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2020.08.005"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-27017-w"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/onco5010008"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/JU.0000000000001363"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1411446111"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.23125"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-49811-w"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-022-01080-4"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes14050956"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-08167-5"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.ccr-21-2577"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.ccr-20-0168"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1902651116"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.cd-21-1547"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.10.025"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-022-01235-4"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2020.07.004"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25147532"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2017.77.6880"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1011652"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.ccr-19-3023"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13112563"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.5652"}],"container-title":["The Prostate"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pros.70042","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T09:20:12Z","timestamp":1762852812000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pros.70042"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9]]},"references-count":27,"journal-issue":{"issue":"16","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1002\/pros.70042"],"URL":"https:\/\/doi.org\/10.1002\/pros.70042","archive":["Portico"],"relation":{},"ISSN":["0270-4137","1097-0045"],"issn-type":[{"value":"0270-4137","type":"print"},{"value":"1097-0045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9]]},"assertion":[{"value":"2025-07-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}