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000294383 1001_ $$aMetzenmacher, Martin$$b0
000294383 245__ $$aMinimally invasive determination of pancreatic ductal adenocarcinoma (PDAC) subtype by means of circulating cell-free RNA.
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000294383 520__ $$aPancreatic ductal adenocarcinoma (PDAC) comprises two clinically relevant molecular subtypes that are currently determined using tissue biopsies, which are spatially biased and highly invasive. We used whole transcriptome sequencing of 10 plasma samples with tumor-informed 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-specific, protein-coding cell-free RNA (cfRNA) transcripts. The subtype specificity of these transcripts was validated in two independent tissue cohorts comprising 195 and 250 cases, respectively. Three disease-relevant cfRNA-defined subtype markers (DEGS1, KDELC1, and RPL23AP7) that consistently associated with basal-like 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.
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000294383 650_7 $$2Other$$aPDAC
000294383 650_7 $$2Other$$acfRNA
000294383 650_7 $$2Other$$aliquid biopsy
000294383 650_7 $$2Other$$asubtype
000294383 650_7 $$2Other$$atherapy
000294383 7001_ $$00000-0002-3813-6961$$aZaun, Gregor$$b1
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000294383 7001_ $$0P:(DE-HGF)0$$aCheung, Phyllis$$b3
000294383 7001_ $$00000-0002-9955-5991$$aReissig, Timm M$$b4
000294383 7001_ $$0P:(DE-He78)3e79424c5bab1c2011182d87880c1796$$aSchürmann, Hendrik$$b5$$udkfz
000294383 7001_ $$avon Neuhoff, Nils$$b6
000294383 7001_ $$aO'Kane, Grainne$$b7
000294383 7001_ $$aRamotar, Stephanie$$b8
000294383 7001_ $$aDodd, Anna$$b9
000294383 7001_ $$aGallinger, Steven$$b10
000294383 7001_ $$0P:(DE-He78)8b642bc1c86616f9a16b7ff392b76a69$$aMuckenhuber, Alexander$$b11$$udkfz
000294383 7001_ $$aKnox, Jennifer J$$b12
000294383 7001_ $$aKunzmann, Volker$$b13
000294383 7001_ $$aHorn, Peter A$$b14
000294383 7001_ $$0P:(DE-He78)c684a26e52cc44716354a4d15f530b4e$$aHoheisel, Jörg$$b15$$udkfz
000294383 7001_ $$0P:(DE-He78)026e0a55b968f360a3c349689ce8a99c$$aSiveke, Jens$$b16$$udkfz
000294383 7001_ $$00000-0002-2776-6706$$aLueong, Smiths S$$b17
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