{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T21:02:13Z","timestamp":1789851733094,"version":"4.0.1"},"reference-count":12,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:00:00Z","timestamp":1789776000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:00:00Z","timestamp":1789776000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Prostate"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>We sought to characterize an LHB\u2010associated tumor transcriptomic state across public prostate cancer datasets. Tumor LHB expression and the correlation\u2010derived signature were treated as molecular measurements only; serum luteinizing hormone and testosterone were not available or analyzed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In 501 TCGA\u2010PRAD tumors, the 25 genes most positively and 25 most negatively correlated with LHB defined a direction\u2010weighted signature. The frozen score was projected without refitting into GSE54460, GSE116918, and two GSE21034 platform views. Cohort\u2010specific grade, biochemical recurrence, and compact expression programs were evaluated. Program genes did not overlap the signature, and LHB was excluded from steroidogenesis. In GSE176031, upper and lower signature\u2010score quartiles were compared within each of 53 samples.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The score was higher in high\u2010grade TCGA\u2010PRAD tumors (mean difference, 0.327; P\u2009=\u20097.12\u2009\u00d7\u200910\n                      <jats:sup>\u22129<\/jats:sup>\n                      ) and had positive but heterogeneous grade differences in the external datasets. Across all five bulk views, the score correlated negatively with androgen receptor signaling (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u2009\u22120.365 to \u22120.627) and positively with cell cycle (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.283\u20130.692) and epithelial\u2010mesenchymal transition (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.217\u20130.734). Direct LHB transcripts were detected in 30 of 53,765 cells. Sample\u2010level single\u2010cell contrasts showed lower androgen receptor signaling and higher cell\u2010cycle and epithelial\u2010mesenchymal\u2010transition scores in signature\u2010high epithelial states; the LHB\u2010excluded steroidogenesis contrast was near zero.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The LHB\u2010correlation\u2010derived signature identifies an AR\u2010low, proliferative, mesenchymal\u2010associated expression state across datasets. It does not measure circulating hormones, establish LHB\u2010dependent biology, or support clinical use. Paired molecular and functional studies are required.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pros.70256","type":"journal-article","created":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T20:10:03Z","timestamp":1789848603000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cross\u2010Cohort Characterization of an LHB\u2010Associated Transcriptomic State in Prostate Cancer"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-2811-5247","authenticated-orcid":false,"given":"Zhihua","family":"Pan","sequence":"first","affiliation":[{"name":"Department of Urology The First Affiliated Hospital with Nanjing Medical University Nanjing Jiangsu China"},{"name":"Department of Urology Dongtai People's Hospital Dongtai Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3618-6400","authenticated-orcid":false,"given":"Jinjiang","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Urology The First Affiliated Hospital with Nanjing Medical University Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Urology The First Affiliated Hospital with Nanjing Medical University Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2891-4130","authenticated-orcid":false,"given":"Ruizhe","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Urology The First Affiliated Hospital with Nanjing Medical University Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaobo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Urology The First Affiliated Hospital with Nanjing Medical University Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Urology The First Affiliated Hospital with Nanjing Medical University Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4705-6445","authenticated-orcid":false,"given":"Bianjiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Urology The First Affiliated Hospital with Nanjing Medical University Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,19]]},"reference":[{"key":"e_1_2_14_2_1","first-page":"293","article-title":"Studies on Prostatic Cancer. 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The Effect of Castration, of Estrogen and of Androgen Injection on Serum Phosphatases in Metastatic Carcinoma of the Prostate","volume":"1","author":"Huggins C.","year":"1941","journal-title":"Cancer Research"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/bco2.70043"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.22899"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.10.025"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-13-2699"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx637"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2010.05.026"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-27322-4"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-11-3004"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-16-2169"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.22901"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.23052"}],"container-title":["The Prostate"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pros.70256","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/pros.70256","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pros.70256","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T20:10:09Z","timestamp":1789848609000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pros.70256"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,19]]},"references-count":12,"alternative-id":["10.1002\/pros.70256"],"URL":"https:\/\/doi.org\/10.1002\/pros.70256","archive":["Portico"],"relation":{},"ISSN":["0270-4137","1097-0045"],"issn-type":[{"value":"0270-4137","type":"print"},{"value":"1097-0045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,19]]},"assertion":[{"value":"2026-07-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"pros.70256"}}