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Minimally invasive determination of pancreatic ductal adenocarcinoma (PDAC) subtype by means of circulating cell‐free RNA
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Minimally invasive determination of pancreatic ductal adenocarcinoma (PDAC) subtype by means of circulating cell‐free RNA
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Minimally invasive determination of pancreatic ductal adenocarcinoma (PDAC) subtype by means of circulating cell‐free RNA
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Journal Article
Minimally invasive determination of pancreatic ductal adenocarcinoma (PDAC) subtype by means of circulating cell‐free RNA
2025
Overview
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. Subtype determination of the two clinically relevant molecular subtypes of pancreatic cancer has exclusively relied on tumor tissue samples, which are unfortunately not always available, require highly invasive procedures to obtain and, owing to tumor heterogeneity, provide limited results. In this proof‐of‐concept study, we deploy next‐generation sequencing and digital PCR to provide evidence for the clinical utility of cell‐free RNA for determination of PDAC subtypes.
Publisher
John Wiley & Sons, Inc,John Wiley and Sons Inc,Wiley
Subject
/ Aged
/ Analysis
/ Biomarkers, Tumor - genetics
/ Biopsy
/ Carcinoma, Pancreatic Ductal - blood
/ Carcinoma, Pancreatic Ductal - diagnosis
/ Carcinoma, Pancreatic Ductal - genetics
/ Carcinoma, Pancreatic Ductal - pathology
/ Cell-Free Nucleic Acids - blood
/ Cell-Free Nucleic Acids - genetics
/ cfRNA
/ Diseases
/ Female
/ Gene Expression Regulation, Neoplastic
/ Humans
/ Male
/ Pancreas
/ Pancreatic Neoplasms - blood
/ Pancreatic Neoplasms - diagnosis
/ Pancreatic Neoplasms - genetics
/ Pancreatic Neoplasms - pathology
/ Patients
/ PDAC
/ Plasma
/ Relapse
/ RNA
/ subtype
/ therapy
/ Tumors
