{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:34:54Z","timestamp":1792794894329,"version":"4.5.0"},"posted":{"date-parts":[[2025,9,25]]},"group-title":"Oncology","reference-count":10,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"name":"Center for Cancer Research, National Cancer Institute, U.S. National Institutes of Health","award":["ZIA BC 011492"],"award-info":[{"award-number":["ZIA BC 011492"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,8,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Malignant mesothelioma is a rare, aggressive malignancy with limited treatment options and few robust prognostic biomarkers. Current blood-based assays (MESOMARK, fibulin-3, osteopontin) are constrained by inconsistent sensitivity and preanalytical instability. Here, we evaluated four urinary metabolites\u2014creatine riboside (CR), N-acetylneuraminic acid (NANA), cortisol sulfate (CS), and 27-nor-5\u03b2-cholestane-3\u03b1,7\u03b1,12\u03b1,24,25-pentol (cholestane pentol, CP)\u2014previously linked to prognosis in lung cancer and intrahepatic cholangiocarcinoma, in a clinically annotated mesothelioma cohort (n=95;\n                  <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT01950572\">NCT01950572<\/jats:ext-link>\n                  ) with paired RNA-sequencing data. All four metabolites correlated positively with a validated 48-gene poor-prognostic gene-expression signature, with a standardized composite score showing the strongest concordance (Spearman R=0.34, p=0.001). Overall survival declined progressively with the number of elevated metabolites, and patients with all four elevated had the poorest prognosis (log-rank p&lt;0.0001). Stratification of the composite score by quartile and by median reproduced this graded effect (p&lt;0.0001 for both), and associations were independent of age, sex, and disease site. Urinary metabolite profiling thus offers a simple, repeatable, noninvasive prognostic tool that complements existing blood-based assays and may support risk stratification, longitudinal monitoring, and clinical-trial enrichment in mesothelioma.\n                <\/jats:p>","DOI":"10.1101\/2025.09.23.25336488","type":"posted-content","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T19:45:14Z","timestamp":1758829514000},"source":"Crossref","is-referenced-by-count":1,"title":["Urinary Metabolite Signatures Stratify Survival in Malignant Mesothelioma: A Noninvasive Prognostic Tool"],"prefix":"10.64898","author":[{"given":"Leila","family":"Toulabi","sequence":"first","affiliation":[{"name":"Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua K.","family":"Stone","sequence":"additional","affiliation":[{"name":"Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Khan","sequence":"additional","affiliation":[{"name":"Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffit","family":"Hassan","sequence":"additional","affiliation":[{"name":"Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Curtis C.","family":"Harris","sequence":"additional","affiliation":[{"name":"Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daxesh P.","family":"Patel","sequence":"additional","affiliation":[{"name":"Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026082002500660000_2025.09.23.25336488v2.1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1912719"},{"key":"2026082002500660000_2025.09.23.25336488v2.2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)14794-0"},{"key":"2026082002500660000_2025.09.23.25336488v2.3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1115050"},{"key":"2026082002500660000_2025.09.23.25336488v2.4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa051185"},{"key":"2026082002500660000_2025.09.23.25336488v2.5","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-14-0109"},{"key":"2026082002500660000_2025.09.23.25336488v2.6","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-19-0453"},{"issue":"2","key":"2026082002500660000_2025.09.23.25336488v2.7","doi-asserted-by":"crossref","first-page":"100938","DOI":"10.1016\/j.xcrm.2023.100938","article-title":"Genomic and transcriptomic analyses identify a prognostic gene signature and predict response to therapy in pleural and peritoneal mesothelioma","volume":"4","year":"2023","journal-title":"Cell Rep. Med"},{"issue":"14","key":"2026082002500660000_2025.09.23.25336488v2.8","doi-asserted-by":"crossref","first-page":"e157410","DOI":"10.1172\/JCI157410","article-title":"Creatine riboside is a cancer cell\u2013derived metabolite associated with arginine auxotrophy","volume":"132","year":"2022","journal-title":"J. Clin. Invest"},{"key":"2026082002500660000_2025.09.23.25336488v2.9","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-020-01126-7"},{"issue":"18","key":"2026082002500660000_2025.09.23.25336488v2.10","doi-asserted-by":"crossref","first-page":"e164599","DOI":"10.1172\/JCI164599","article-title":"Tumors produce glucocorticoids by metabolite recycling, not synthesis, and activate Tregs to promote growth","volume":"133","year":"2023","journal-title":"J. Clin. Invest"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.09.23.25336488","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T09:50:13Z","timestamp":1787219413000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.1101\/2025.09.23.25336488"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,25]]},"references-count":10,"URL":"https:\/\/doi.org\/10.1101\/2025.09.23.25336488","relation":{},"subject":[],"published":{"date-parts":[[2025,9,25]]},"subtype":"preprint"}}