Cell free RNA detection of pancreatic cancer in pre diagnostic high risk and symptomatic patients

Travis W. Moore, Elias Spiliotopoulos, Rowan L. Callahan, C. Ward Kirschbaum, Conner F. Bailey, Hyun Ji Kim, Breeshey Roskams-Hieter, Florian Goncalves, Dove Keith, Aaron J. Grossberg, Paul T. Spellman, Gordon B. Mills, Rosalie C. Sears, Terry K. Morgan and Thuy T. M. Ngo ()
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Travis W. Moore: Oregon Health and Science University
Elias Spiliotopoulos: Oregon Health and Science University
Rowan L. Callahan: Oregon Health and Science University
C. Ward Kirschbaum: Oregon Health and Science University
Conner F. Bailey: Oregon Health and Science University
Hyun Ji Kim: Oregon Health and Science University
Breeshey Roskams-Hieter: Oregon Health and Science University
Florian Goncalves: Oregon Health and Science University
Dove Keith: Oregon Health and Science University
Aaron J. Grossberg: Oregon Health and Science University
Paul T. Spellman: Oregon Health and Science University
Gordon B. Mills: Oregon Health and Science University
Rosalie C. Sears: Oregon Health and Science University
Terry K. Morgan: Oregon Health and Science University
Thuy T. M. Ngo: Oregon Health and Science University

Nature Communications, 2025, vol. 16, issue 1, 1-12

Abstract: Abstract Pancreatic ductal adenocarcinomas (PDAC) are among the most fatal cancers, in part due to frequent detection at advanced stages. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), the most sensitive diagnostic method of PDAC in current standard clinical practice, is invasive, costly, with access limited to major healthcare settings. Here, we present a non-invasive evaluation of plasma cell-free RNA (cfRNA) for PDAC detection in pre-diagnostic high-risk and de novo symptomatic patients presenting for EUS-FNA. We develop a cfRNA normalization method to account for preanalytical variation and handling effects and derive 29 potential cfRNA biomarkers for PDAC diagnosis using 153 samples collected prior to the EUS procedure. Biomarkers related to liver function are elevated in PDAC samples, including early-stage patients without liver metastasis. Classification of PDAC using these biomarkers is validated using an independent cohort of 95 samples. Our findings could help to improve diagnostic utility in high-risk and symptomatic individuals.

Date: 2025
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DOI: 10.1038/s41467-025-62685-y

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