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We used whole transcriptome sequencing of 10 plasma samples with tumor\u2010informed subtypes, complemented by proteomic analysis for minimally invasive identification of PDAC subtype markers. Data were validated in independent large cohorts and correlated with treatment response and patient outcome. Differential transcript abundance analyses revealed 32 subtype\u2010specific, protein\u2010coding cell\u2010free RNA (cfRNA) transcripts. The subtype specificity of these transcripts was validated in two independent tissue cohorts comprising 195 and 250 cases, respectively. Three disease\u2010relevant cfRNA\u2010defined subtype markers (\n                    <jats:italic>DEGS1<\/jats:italic>\n                    ,\n                    <jats:italic>KDELC1<\/jats:italic>\n                    , and\n                    <jats:italic>RPL23AP7<\/jats:italic>\n                    ) that consistently associated with basal\u2010like tumors across all cohorts were identified. In both tumor and liquid biopsies, the overexpression of these markers correlated with poor survival. Moreover, elevated levels of the identified markers were linked to a poor response to systemic therapy and early relapse in resected patients. Our data indicate clinical applicability of cfRNA markers in determining tumor subtypes and monitoring disease recurrence.\n                  <\/jats:p>","DOI":"10.1002\/1878-0261.13747","type":"journal-article","created":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T04:41:12Z","timestamp":1730349672000},"page":"357-376","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Minimally invasive determination of pancreatic ductal adenocarcinoma (\n                    <scp>PDAC<\/scp>\n                    ) subtype by means of circulating cell\u2010free\n                    <scp>RNA<\/scp>"],"prefix":"10.1002","volume":"19","author":[{"given":"Martin","family":"Metzenmacher","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, West German Cancer Center University Hospital Essen  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