An intron retention-derived secreted Endoglin Isoform as a circulating biomarker in pancreatic ductal adenocarcinoma.
6 affiliations
- 1Department of Pharmacology, University of Arizona, Tucson, AZ, 85724, USA.
- 2Department of Cellular & Molecular Medicine, University of Arizona, Tucson, AZ, 85724, USA.
- 3Department of Medicine, University of Arizona, Tucson, AZ, 85724, USA.
- 4Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
- 5Division of Hematology/Oncology, University of Pittsburgh, Pittsburgh, PA, 15261, USA.
- 6Department of Pharmacology, University of Arizona, Tucson, AZ, 85724, USA; Comprehensive Cancer Center, University of Arizona, Tucson, AZ, 85724, USA. Electronic address: [email protected].
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with few effective strategies for early detection or prognostic assessment. Endoglin (CD105) is an endothelial receptor best known for its roles in vascular development and tumor angiogenesis, and its only recognized circulating form arises through proteolytic shedding of the full-length receptor. Here, we report a pancreatic tumor-derived secreted endoglin isoform that is molecularly distinct from all known endoglin variants, enabling the development of an isoform-specific antibody for selective detection. Through integrated transcriptomic, biochemical, and translational analyses, we identified a truncated endoglin isoform generated by intron retention that contains a unique C-terminal peptide absent from canonical endoglin. This isoform was detected in human PDAC cell lines, orthotopic xenografts, primary patient tumors, patient sera, and the KPC genetically engineered mouse model, demonstrating conservation across clinically relevant systems. Tissue microarray analysis revealed that the isoform is prevalent in PDAC and represents a major subset of endoglin-positive tumors, while immunoprecipitation and a newly developed sandwich ELISA confirmed its presence in patient circulation, supporting its potential as a blood-based biomarker. Together, these findings identify a previously unrecognized, tumor-derived secreted endoglin isoform and highlight intron retention as source of circulating protein biomarkers in pancreatic cancer.
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BibTeX
@article{ortiz2026intron,
title = {{An intron retention-derived secreted Endoglin Isoform as a circulating biomarker in pancreatic ductal adenocarcinoma.}},
author = {Hannah R Ortiz and Julia Podgorski and Monique R Archuleta and Atsushi Ishii and Aaron Ramonett and Christopher Cartmell and Nathan A Ellis and Paul R Langlais and Karthikeyan Mythreye and Nadine Hempel and Nam Y Lee},
journal = {Neoplasia (New York, N.Y.)},
year = {2026},
month = oct,
doi = {10.1016/j.neo.2026.101379},
url = {https://europepmc.org/article/MED/42854278},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - An intron retention-derived secreted Endoglin Isoform as a circulating biomarker in pancreatic ductal adenocarcinoma.
AU - Hannah R Ortiz
AU - Julia Podgorski
AU - Monique R Archuleta
AU - Atsushi Ishii
AU - Aaron Ramonett
AU - Christopher Cartmell
AU - Nathan A Ellis
AU - Paul R Langlais
AU - Karthikeyan Mythreye
AU - Nadine Hempel
AU - Nam Y Lee
PY - 2026
DA - 2026/10/09
JO - Neoplasia (New York, N.Y.)
DO - 10.1016/j.neo.2026.101379
UR - https://europepmc.org/article/MED/42854278
AB - Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with few effective strategies for early detection or prognostic assessment. Endoglin (CD105) is an endothelial receptor best known for its roles in vascular development and tumor angiogenesis, and its only recognized circulating form arises through proteolytic shedding of the full-length receptor. Here, we report a pancreatic tumor-derived secreted endoglin isoform that is molecularly distinct from all known endoglin variants, enabling the development of an isoform-specific antibody for selective detection. Through integrated transcriptomic, biochemical, and translational analyses, we identified a truncated endoglin isoform generated by intron retention that contains a unique C-terminal peptide absent from canonical endoglin. This isoform was detected in human PDAC cell lines, orthotopic xenografts, primary patient tumors, patient sera, and the KPC genetically engineered mouse model, demonstrating conservation across clinically relevant systems. Tissue microarray analysis revealed that the isoform is prevalent in PDAC and represents a major subset of endoglin-positive tumors, while immunoprecipitation and a newly developed sandwich ELISA confirmed its presence in patient circulation, supporting its potential as a blood-based biomarker. Together, these findings identify a previously unrecognized, tumor-derived secreted endoglin isoform and highlight intron retention as source of circulating protein biomarkers in pancreatic cancer.
SN - 1522-8002
SN - 1476-5586
ER -