Minimally invasive determination of pancreatic ductal adenocarcinoma (PDAC) subtype by means of circulating cell‐free RNA
Pancreatic 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...
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| Language: | English |
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Wiley
2025-02-01
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| Series: | Molecular Oncology |
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| Online Access: | https://doi.org/10.1002/1878-0261.13747 |
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| author | Martin Metzenmacher Gregor Zaun Marija Trajkovic‐Arsic Phyllis Cheung Timm M. Reissig Hendrik Schürmann Nils vonNeuhoff Grainne O'Kane Stephanie Ramotar Anna Dodd Steven Gallinger Alexander Muckenhuber Jennifer J. Knox Volker Kunzmann Peter A. Horn Jörg D. Hoheisel Jens T. Siveke Smiths S. Lueong |
| author_facet | Martin Metzenmacher Gregor Zaun Marija Trajkovic‐Arsic Phyllis Cheung Timm M. Reissig Hendrik Schürmann Nils vonNeuhoff Grainne O'Kane Stephanie Ramotar Anna Dodd Steven Gallinger Alexander Muckenhuber Jennifer J. Knox Volker Kunzmann Peter A. Horn Jörg D. Hoheisel Jens T. Siveke Smiths S. Lueong |
| author_sort | Martin Metzenmacher |
| collection | DOAJ |
| description | Pancreatic 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. |
| format | Article |
| id | doaj-art-04ea8a62df7a4b7e8097554b6dc9af8f |
| institution | Kabale University |
| issn | 1574-7891 1878-0261 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj-art-04ea8a62df7a4b7e8097554b6dc9af8f2025-02-04T17:30:20ZengWileyMolecular Oncology1574-78911878-02612025-02-0119235737610.1002/1878-0261.13747Minimally invasive determination of pancreatic ductal adenocarcinoma (PDAC) subtype by means of circulating cell‐free RNAMartin Metzenmacher0Gregor Zaun1Marija Trajkovic‐Arsic2Phyllis Cheung3Timm M. Reissig4Hendrik Schürmann5Nils vonNeuhoff6Grainne O'Kane7Stephanie Ramotar8Anna Dodd9Steven Gallinger10Alexander Muckenhuber11Jennifer J. Knox12Volker Kunzmann13Peter A. Horn14Jörg D. Hoheisel15Jens T. Siveke16Smiths S. Lueong17Department of Medical Oncology, West German Cancer Center University Hospital Essen GermanyDepartment of Medical Oncology, West German Cancer Center University Hospital Essen GermanyGerman Cancer Consortium (DKTK), partner site Essen/Düsseldorf, a partnership between German Cabcer Research Center (DKFZ) and University Hospital Essen GermanyGerman Cancer Consortium (DKTK), partner site Essen/Düsseldorf, a partnership between German Cabcer Research Center (DKFZ) and University Hospital Essen GermanyDepartment of Medical Oncology, West German Cancer Center University Hospital Essen GermanyDepartment of Medical Oncology, West German Cancer Center University Hospital Essen GermanyDepartment of Pediatric Hematology and Oncology, Department for Pediatrics III University Hospital of Essen GermanyPanCuRx Translational Research Initiative Ontario Institute for Cancer Research Toronto CanadaPanCuRx Translational Research Initiative Ontario Institute for Cancer Research Toronto CanadaPanCuRx Translational Research Initiative Ontario Institute for Cancer Research Toronto CanadaPanCuRx Translational Research Initiative Ontario Institute for Cancer Research Toronto CanadaInstitute of Pathology Technical University of Munich GermanyPanCuRx Translational Research Initiative Ontario Institute for Cancer Research Toronto CanadaDepartment of Internal Medicine II, Medical Oncology, Comprehensive Cancer Center Mainfranken Würzburg University Hospital Würzburg GermanyInstitute for Transfusion Medicine University Hospital of Essen GermanyDivision of Functional Genome Analysis German Cancer Research Center (DKFZ) Heidelberg GermanyGerman Cancer Consortium (DKTK), partner site Essen/Düsseldorf, a partnership between German Cabcer Research Center (DKFZ) and University Hospital Essen GermanyGerman Cancer Consortium (DKTK), partner site Essen/Düsseldorf, a partnership between German Cabcer Research Center (DKFZ) and University Hospital Essen GermanyPancreatic 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.https://doi.org/10.1002/1878-0261.13747cfRNAliquid biopsyPDACsubtypetherapy |
| spellingShingle | Martin Metzenmacher Gregor Zaun Marija Trajkovic‐Arsic Phyllis Cheung Timm M. Reissig Hendrik Schürmann Nils vonNeuhoff Grainne O'Kane Stephanie Ramotar Anna Dodd Steven Gallinger Alexander Muckenhuber Jennifer J. Knox Volker Kunzmann Peter A. Horn Jörg D. Hoheisel Jens T. Siveke Smiths S. Lueong Minimally invasive determination of pancreatic ductal adenocarcinoma (PDAC) subtype by means of circulating cell‐free RNA Molecular Oncology cfRNA liquid biopsy PDAC subtype therapy |
| title | Minimally invasive determination of pancreatic ductal adenocarcinoma (PDAC) subtype by means of circulating cell‐free RNA |
| title_full | Minimally invasive determination of pancreatic ductal adenocarcinoma (PDAC) subtype by means of circulating cell‐free RNA |
| title_fullStr | Minimally invasive determination of pancreatic ductal adenocarcinoma (PDAC) subtype by means of circulating cell‐free RNA |
| title_full_unstemmed | Minimally invasive determination of pancreatic ductal adenocarcinoma (PDAC) subtype by means of circulating cell‐free RNA |
| title_short | Minimally invasive determination of pancreatic ductal adenocarcinoma (PDAC) subtype by means of circulating cell‐free RNA |
| title_sort | minimally invasive determination of pancreatic ductal adenocarcinoma pdac subtype by means of circulating cell free rna |
| topic | cfRNA liquid biopsy PDAC subtype therapy |
| url | https://doi.org/10.1002/1878-0261.13747 |
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