{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T12:08:10Z","timestamp":1791634090258,"version":"4.3.4"},"reference-count":57,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T00:00:00Z","timestamp":1740700800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>To determine the performance of a multi-gene copy number variation (MG-CNV) risk score in metastatic tissue and plasma biospecimens from treatment-na\u00efve metastatic castration-resistant prostate cancer (mCRPC) patients for prediction of clinical outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The mCRPC tissue and plasma cell-free DNA (cfDNA) biospecimen sequencing results obtained from publicly accessed cohorts in dbGaP, cBioPortal, and an institutional mCRPC cohort were used to develop a MG-CNV risk score derived from gains in AR, MYC, COL22A1, PIK3CA, PIK3CB, NOTCH1 and losses in TMPRSS2, NCOR1, ZBTB16, TP53, NKX3-1 in independent cohorts for determining overall survival (OS), progression-free survival (PFS) to first-line androgen receptor pathway inhibitors (ARPIs). The range of the risk scores for each cohort was dichotomized into \u201chigh-risk\u201d and \u201clow-risk\u201d groups and association with OS\/PFS determined. Univariate and multivariable Cox proportional hazards regressions were applied for survival analyses (P\u2009&amp;lt;\u2009.05 for statistical significance).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of 1137 metastatic tissue-plasma biospecimens across all cohorts, 699\/1137 were treatment-naive mCRPC (235\/699 metastatic tissue; 464\/699 plasma-cfDNA), and 311\/1137 were matched tissue-cfDNA pairs. In multivariable analysis, the MG-CNV risk score derived from metastatic tissue or in cfDNA was statistically significantly associated with OS with high score associated with short survival (hazard ratio = 2.65, confidence interval = 1.99 to 3.51; P\u2009=\u20091.35\u221211) and shorter PFS to ARPIs (median PFS of 7.8\u2009months) compared with 14\u2009months in patients with low-risk score.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>A molecular risk score in treatment-na\u00efve mCRPC state obtained either in metastatic tissue or cfDNA predicts clinical survival outcomes and offers a tumor biology-based tool to design biomarker-based enrichment clinical trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jncics\/pkaf025","type":"journal-article","created":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T15:45:30Z","timestamp":1740498330000},"source":"Crossref","is-referenced-by-count":5,"title":["Multi-gene risk score for prediction of clinical outcomes in treatment-na\u00efve metastatic castrate-resistant prostate cancer"],"prefix":"10.1093","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3111-8090","authenticated-orcid":false,"given":"Muhammad Zaki Hidayatullah","family":"Fadlullah","sequence":"first","affiliation":[{"name":"Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah , Salt Lake City, UT,","place":["United States"]},{"name":"Department of Biomedical Informatics, Huntsman Cancer Institute, University of Utah , Salt Lake City, UT,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3383-8582","authenticated-orcid":false,"given":"David","family":"Nix","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, Huntsman Cancer Institute, University of Utah , Salt Lake City, UT,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9929-8374","authenticated-orcid":false,"given":"Cameron","family":"Herberts","sequence":"additional","affiliation":[{"name":"Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia , Vancouver, BC,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4455-4497","authenticated-orcid":false,"given":"Corinne","family":"Maurice-Dror","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, BC Cancer , Vancouver, BC,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2399-0329","authenticated-orcid":false,"given":"Alexander W","family":"Wyatt","sequence":"additional","affiliation":[{"name":"Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia , Vancouver, BC,","place":["Canada"]},{"name":"Michael Smith Genome Sciences Centre, BC Cancer , Vancouver, BC,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1233-1638","authenticated-orcid":false,"given":"Bogdana","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Division of Urology, Department of Surgery, Huntsman Cancer Institute, University of Utah , Salt Lake City, UT,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brayden","family":"Fairbourn","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Spencer Fox Eccles School of Medicine , Salt Lake City, UT,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2955-8369","authenticated-orcid":false,"given":"Aik-Choon","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah , Salt Lake City, UT,","place":["United States"]},{"name":"Department of Biomedical Informatics, Huntsman Cancer Institute, University of Utah , Salt Lake City, UT,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9364-8572","authenticated-orcid":false,"given":"Liang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Tumor Biology, H. 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