{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T02:23:38Z","timestamp":1740104618221,"version":"3.37.3"},"reference-count":50,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T00:00:00Z","timestamp":1713830400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>It is important to identify molecular features that improve prostate cancer (PCa) risk stratification before radical treatment with curative intent. Molecular analysis of historical diagnostic formalin\u2010fixed paraffin\u2010embedded (FFPE) prostate biopsies from cohorts with post\u2010radiotherapy (RT) long\u2010term clinical follow\u2010up has been limited. Utilizing parallel sequencing modalities, we performed a proof\u2010of\u2010principle sequencing analysis of historical diagnostic FFPE prostate biopsies. We compared patients with (i) stable PCa (sPCa)\u00a0postprimary or salvage RT,\u00a0(ii) progressing PCa (pPCa) post\u2010RT,\u00a0and (iii) de novo metastatic PCa\u00a0(mPCa).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A cohort of 19 patients with diagnostic prostate biopsies (<jats:italic>n<\/jats:italic>\u2009=\u20096 sPCa, <jats:italic>n<\/jats:italic>\u2009=\u20095 pPCa, <jats:italic>n<\/jats:italic>\u2009=\u20098 mPCa) and mean 4 years 10 months follow\u2010up (diagnosed 2009\u20132016) underwent nucleic acid extraction from demarcated malignancy. Samples underwent 3\u2032RNA sequencing (3\u2032RNAseq) (<jats:italic>n<\/jats:italic>\u2009=\u200919), nanoString analysis (<jats:italic>n<\/jats:italic>\u2009=\u200912), and Illumina 850k methylation (<jats:italic>n<\/jats:italic>\u2009=\u20098) sequencing. Bioinformatic analysis was performed to coherently identify differentially expressed genes and methylated genomic regions (MGRs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Eighteen of 19 samples provided useable 3\u2032RNAseq data. Principal component analysis (PCA) demonstrated similar expression profiles between pPCa and mPCa cases, versus sPCa. Coherently differentially methylated probes between these groups identified ~600 differentially MGRs. The top 50 genes with increased expression in pPCa patients were associated with reduced progression\u2010free survival post\u2010RT (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001) in an external cohort.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>3\u2032RNAseq, nanoString and 850k\u2010methylation analyses are each achievable from historical FFPE diagnostic pretreatment prostate biopsies, unlocking the potential to utilize large cohorts of historic clinical samples. Profiling similarities between individuals with pPCa and mPCa suggests biological similarities and historical radiological staging limitations, which warrant further investigation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pros.24715","type":"journal-article","created":{"date-parts":[[2024,4,24]],"date-time":"2024-04-24T04:20:21Z","timestamp":1713932421000},"page":"977-990","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular analysis of archival diagnostic prostate cancer biopsies identifies genomic similarities in cases with progression post\u2010radiotherapy, and those with de novo metastatic\u00a0disease"],"prefix":"10.1002","volume":"84","author":[{"given":"Philip Vincent","family":"Charlton","sequence":"first","affiliation":[{"name":"Department of Oncology University of Oxford Oxford UK"},{"name":"Department of Oncology Oxford University Hospitals NHS Foundation Trust Oxford 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