{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T10:49:25Z","timestamp":1791802165859,"version":"4.3.4"},"reference-count":24,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T00:00:00Z","timestamp":1788048000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T00:00:00Z","timestamp":1788048000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U54 HG013243"],"award-info":[{"award-number":["U54 HG013243"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01CA263494"],"award-info":[{"award-number":["R01CA263494"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01CA293883"],"award-info":[{"award-number":["U01CA293883"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U24DK132746"],"award-info":[{"award-number":["U24DK132746"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U24DK132740"],"award-info":[{"award-number":["U24DK132740"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Previous genome\u2010wide association studies have identified more than 400 prostate cancer (PCa) susceptibility loci. However, the tissue and spatial epithelial contexts through which inherited PCa risk may operate in the normal prostate remain incompletely understood. We analyzed normal human prostate spatial transcriptomic data using a gsMap\u2010based framework to localize PCa association signals across spatially resolved prostate compartments. Spatial spots were clustered using SpaGCN and then manually curated and annotated based on matched histological images and canonical prostate marker gene expression. Because individual spatial spots may contain multiple cells, annotations were interpreted as compartment\u2010enriched dominants rather than pure cell\u2010type identities. PCa genetic association scores were aggregated within annotated compartments using Cauchy\u2010combined\n                    <jats:italic>p<\/jats:italic>\n                    value and median spot\u2010level\n                    <jats:italic>p<\/jats:italic>\n                    value as a complementary descriptive summary. Gene\u2010level spatial correspondence was further assessed using Pearson correlation coefficients (PCCs) between gene\u2010expression patterns and spot\u2010level PCa gsMap signal. We annotated normal prostate tissue into four major compartments: basal epithelium\u2010enriched, luminal epithelium\u2010enriched, smooth muscle\u2010enriched, and fibroblast stroma\u2010enriched compartments. Basal epithelium\u2010enriched compartments showed the strongest and most consistent enrichment for PCa association, with a Cauchy\u2010combined\n                    <jats:italic>p<\/jats:italic>\n                    of 1.85\u2009\u00d7\u200910\n                    <jats:sup>\u22128<\/jats:sup>\n                    and a median spot\u2010level based\n                    <jats:italic>p<\/jats:italic>\n                    of 3.67\u2009\u00d7\u200910\n                    <jats:sup>\u22127<\/jats:sup>\n                    . Luminal epithelium\u2010enriched compartments also showed strong enrichment, with a Cauchy\n                    <jats:italic>p<\/jats:italic>\n                    of 3.79\u2009\u00d7\u200910\n                    <jats:sup>\u22127<\/jats:sup>\n                    and a median\u2010based\n                    <jats:italic>p<\/jats:italic>\n                    of 1.45\u2009\u00d7\u200910\n                    <jats:sup>\u22126<\/jats:sup>\n                    . In contrast, fibroblast stroma\u2010enriched compartments showed no evidence of enrichment (Cauchy\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.52; median\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.42), while smooth muscle\u2010enriched compartments showed only modest evidence in the Cauchy\u2010based analysis that was accompanied by a weaker median spot\u2010level association signal (Cauchy\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20098.95\u2009\u00d7\u200910\n                    <jats:sup>\u22124<\/jats:sup>\n                    ; median\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.18). PCC analysis showed that genes with the strongest spatial correspondence to PCa gsMap signal were predominantly epithelial\u2010associated, including\n                    <jats:italic>CDH1<\/jats:italic>\n                    ,\n                    <jats:italic>VAMP8<\/jats:italic>\n                    ,\n                    <jats:italic>GMNN<\/jats:italic>\n                    ,\n                    <jats:italic>TSPAN1<\/jats:italic>\n                    , and\n                    <jats:italic>FOXA1<\/jats:italic>\n                    . In normal human prostate tissue, inherited PCa association localizes preferentially to basal epithelium\u2010enriched and luminal epithelial\u2010enriched compartments rather than to smooth muscle\u2010enriched or fibroblast stroma\u2010enriched compartments. Gene\u2010level PCC patterns further support spatial alignment between PCa\u2010associated gsMap signal and epithelial transcriptional programs. These findings provide proof\u2010of\u2010concept evidence for the spatial localization of inherited PCa susceptibility through the integration of large\u2010scale population\u2010based genetic data and spatial transcriptomics.\n                  <\/jats:p>","DOI":"10.1002\/mc.70175","type":"journal-article","created":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T18:37:56Z","timestamp":1788115076000},"page":"1509-1515","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Spatial Genetic Mapping of Normal Human Prostate Tissue Identifies Epithelial Compartments Enriched for Prostate Cancer Association"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2244-2216","authenticated-orcid":false,"given":"Shuai","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Interdisciplinary Oncology and Department of Genetics, LSU\u2010LCMC Health Cancer Center, School of Medicine Louisiana State University Health Sciences Center New Orleans Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Owen T. M.","family":"Chan","sequence":"additional","affiliation":[{"name":"Pathology Core University of Hawaii Cancer Center, University of Hawaii at Manoa Honolulu Hawaii USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9358-1582","authenticated-orcid":false,"given":"Hua","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Interdisciplinary Oncology and Department of Genetics, LSU\u2010LCMC Health Cancer Center, School of Medicine Louisiana State University Health Sciences Center New Orleans Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Shahabi","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Colorado Anschutz Medical Campus Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9938-3627","authenticated-orcid":false,"given":"Lang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Interdisciplinary Oncology and Department of Genetics, LSU\u2010LCMC Health Cancer Center, School of Medicine Louisiana State University Health Sciences Center New Orleans Louisiana USA"},{"name":"Epidemiology and Population Health Program School of Public Health, Louisiana State University Health Sciences Center New Orleans Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Interdisciplinary Oncology and Department of Genetics, LSU\u2010LCMC Health Cancer Center, School of Medicine Louisiana State University Health Sciences Center New Orleans Louisiana USA"},{"name":"Bioinformatics and Genomics Core School of Medicine, Louisiana State University Health Sciences Center New Orleans Louisiana 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