{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T07:08:24Z","timestamp":1778742504240,"version":"3.51.4"},"reference-count":34,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["T32 CA009001"],"award-info":[{"award-number":["T32 CA009001"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>A key clinical challenge in prostate cancer is the identification and validation of biomarkers with high specificity for indolent long\u2010term outcomes. We applied a novel statistical method to identify tumor transcriptomic biomarkers that optimally predicted patients with low metastatic potential.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Using tumor whole\u2010transcriptome data from the Health Professionals Follow\u2010up Study (HPFS, discovery set) and Physicians' Health Study (PHS, validation set), we compared patients who died of prostate cancer or developed metastases (\u201clethal,\u201d\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009113) and patients with &gt;\u20098 years of metastasis\u2010free survival (\u201cindolent,\u201d\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009291). Whole transcriptome tumor gene expression data were generated using an Affymetrix array. We applied a novel method for optimizing a partial area under the curve (pAUC) that up\u2010weighted indolent cases with a predefined 80%\u2013100% specificity. This method leverages weighted logistic lasso regression, with weights chosen via cross\u2010validation to reduce overfitting.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Median age at cancer diagnosis was 66 years; median follow\u2010up for outcomes was 14 years. We identified a 40\u2010gene transcriptome signature of indolent prostate cancer, which, compared to Gleason grade groups, improved the pAUC over the predefined 80%\u2013100% specificity range by 1.72\u2010fold (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and improved overall AUC from 0.85 to 0.93 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). The signature improved positive predictive value for indolent tumors &gt;\u20092\u2010fold with minimal decrease in negative predictive value. Importantly, the 40\u2010gene signature showed high discrimination among intermediate Gleason 7 tumors (Grade groups 2 and 3, AUC 0.88, 95% CI: 0.79\u20130.95).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Incorporating pAUC into prognostic signature development improved identification of prostate tumors with low risk of metastatic potential. Its clinical application may help reduce overtreatment and overdiagnosis of indolent prostate cancers, and the pAUC may be relevant beyond prostate cancer.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pros.70189","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T13:51:32Z","timestamp":1777470692000},"page":"1075-1082","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Gene Expression Tumor Signature Optimizing Partial Area\u2010Under\u2010the\u2010Curve (pAUC) to Improve Specificity for Indolent Prostate Cancer"],"prefix":"10.1002","volume":"86","author":[{"given":"Travis A.","family":"Gerke","sequence":"first","affiliation":[{"name":"Prostate Cancer Clinical Trials Consortium, Memorial Sloan Kettering Cancer Center New York New York USA"},{"name":"Department of Epidemiology Harvard T.H. Chan School of Public Health Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Svitlana","family":"Tyekucheva","sequence":"additional","affiliation":[{"name":"Department of Data Science Dana\u2010Farber Cancer Institute Boston Massachusetts USA"},{"name":"Department of Biostatistics Harvard T.H. Chan School of Public Health Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Konrad H.","family":"Stopsack","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Harvard T.H. Chan School of Public Health Boston Massachusetts USA"},{"name":"Department of Epidemiologic Methods and Etiologic Research Leibniz Institute for Prevention Research and Epidemiology \u2013 BIPS Bremen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0398-6018","authenticated-orcid":false,"given":"Christopher J.","family":"Sweeney","sequence":"additional","affiliation":[{"name":"South Australian Immunogenomics Cancer Center University of Adelaide Adelaide Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosina T.","family":"Lis","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Dana\u2010Farber Cancer Institute Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9917-9981","authenticated-orcid":false,"given":"Elizabeth N.","family":"Westling","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Harvard T.H. Chan School of Public Health Boston Massachusetts USA"},{"name":"Elson S. Floyd College of Medicine Washington State University Spokane Washington USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimo","family":"Loda","sequence":"additional","affiliation":[{"name":"Department of Pathology Weill Cornell Medical Center New York New York USA"},{"name":"Nuffield Department of Surgical Sciences University of Oxford Oxford UK"},{"name":"Dana\u2010Farber Cancer Institute, Harvard Medical School Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meir J.","family":"Stampfer","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Harvard T.H. Chan School of Public Health Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathryn L.","family":"Penney","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Harvard T.H. 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