Minimally invasive determination of pancreatic ductal adenocarcinoma ( <scp>PDAC</scp> ) subtype by means of circulating cell‐free <scp>RNA</scp>
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.
Authors
- Smiths Lueong (ORCID: https://orcid.org/0000-0002-2776-6706)
- Martin Metzenmacher (ORCID: https://orcid.org/0000-0001-5395-9010)
- Timm M. Reißig (ORCID: https://orcid.org/0000-0002-9955-5991)
- Steven Gallinger (ORCID: https://orcid.org/0000-0002-6998-9414)
- Grainne M. O’Kane (ORCID: https://orcid.org/0000-0002-8690-403X)
- Jörg D. Hoheisel (ORCID: https://orcid.org/0000-0002-1583-5049)
- Nils von Neuhoff (ORCID: https://orcid.org/0000-0003-4138-5341)
- Anna Dodd (ORCID: https://orcid.org/0000-0003-0649-0760)
- Hendrik Schürmann
- Marija Trajkovic‐Arsic (ORCID: https://orcid.org/0000-0002-0791-0248)
- Phyllis F. Cheung (ORCID: https://orcid.org/0000-0002-0075-5679)
- Gregor Zaun (ORCID: https://orcid.org/0000-0002-3813-6961)
- Alexander Muckenhuber (ORCID: https://orcid.org/0000-0002-0414-1797)
- Jennifer J. Knox (ORCID: https://orcid.org/0000-0003-3474-6647)
- Volker Kunzmann (ORCID: https://orcid.org/0000-0002-3615-7566)
- Jens Thomas Siveke (ORCID: https://orcid.org/0000-0002-8772-4778)
- Stephanie Ramotar (ORCID: https://orcid.org/0000-0001-7619-2684)
- Péter Horn (ORCID: https://orcid.org/0000-0003-2505-6441)
Institutions
- Ontario Institute for Cancer Research (CA)
- University Health Network (CA)
- German Cancer Research Center (DE)
- Heidelberg University (DE)
- Princess Margaret Cancer Centre (CA)
- Düsseldorf University Hospital (DE)
- Comprehensive Cancer Center Mainfranken (DE)
- Essen University Hospital (DE)
- Universitätsklinikum Würzburg (DE)
- Deutsches Konsortium für Translationale Krebsforschung (DE)
- Heinrich Heine University Düsseldorf (DE)
- University of Duisburg-Essen (DE)
- Technical University of Munich (DE)
Publication Details
- Journal
- Molecular Oncology
- Published
- 2024-10-31
- DOI
- https://doi.org/10.1002/1878-0261.13747
- Citations
- 3
- Primary Topic
- Pancreatic and Hepatic Oncology Research
- Type
- article
- Field-Weighted Citation Impact
- 0.85
Funders
- Takeda Pharmaceutical Company
- Deutsche Forschungsgemeinschaft
- Bundesministerium für Bildung und Forschung
- Universität Duisburg-Essen
- Deutschen Konsortium für Translationale Krebsforschung