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Confirmatory Clinical Validation of a Serum-Based Biomarker Signature for Detection of Early-Stage Pancreatic Ductal Adenocarcinoma
by
, , , , , and
Patricio M. Polanco
1, 
Tamas Gonda
2,
Erkut Borazanci
3,
Evan S. Glazer
4,
Jose G. Trevino
5, 
George DeMuth
6,
Lisa Ford
7,
Thomas King
7,
Norma A. Palma
7,* and
Randall E. Brand
8 1
Division of Surgical Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
2
Division of Gastroenterology & Hepatology, New York University, New York, NY 10016, USA
3
Department of Oncology, HonorHealth Research Institute, Scottsdale, AZ 10510, USA
4
Division of Surgical Oncology, University of Tennessee Health Science Center, Memphis, TN 38163, USA
5
Division of Surgical Oncology, School of Medicine and Surgeons, Virginia Commonwealth University, Richmond, VA 23298, USA
6
Stat One, LLC, Morrisville, NC 27560, USA
7
Immunovia, Inc., Durham, NC 27713, USA
8
Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA 15261, USA
*
Author to whom correspondence should be addressed.
Curr. Oncol. 2025, 32(11), 638; https://doi.org/10.3390/curroncol32110638 (registering DOI)
Submission received: 16 October 2025
/
Revised: 7 November 2025
/
Accepted: 9 November 2025
/
Published: 13 November 2025
(This article belongs to the Section Gastrointestinal Oncology)
Simple Summary
Pancreatic ductal adenocarcinoma (PDAC) has one of the lowest 5-year survival rates of all malignancies, mainly because most cases are diagnosed at late stages. Diagnosing PDAC during early stages (Stage I and II) significantly improves patient survival. To aid in the early detection of PDAC, we developed and clinically validated a serum biomarker signature to distinguish early-stage PDAC in those at high risk of developing the disease. In this study, we performed a second validation of the signature in an independent group of people who were either recently diagnosed with Stage I or II PDAC or were at higher risk of developing PDAC due to a gene mutation, strong family history of PDAC, and/or a mucinous pancreatic cyst. The biomarker signature detected PDAC with high sensitivity and specificity, showing that it has potential to aid in early detection of this malignancy.
Abstract
Early detection of pancreatic ductal adenocarcinoma (PDAC) could extend patient survival, and biomarkers to facilitate this are urgently needed. Here, we performed a second independent validation of PancreaSure, a 5-plex serum biomarker signature to detect early-stage PDAC in high-risk individuals. In contrast to the first validation, this study’s cohort was preemptively balanced for age and sex and only included samples stored for fewer than 5 years. The primary endpoint was to measure test sensitivity against the performance target of 65%. Measuring specificity against the performance target of 90% and comparing test performance to that of carbohydrate antigen 19-9 (CA 19-9) alone were secondary endpoints. Signature analytes were retrospectively measured in serum from a blinded independent cohort of Stage I and II PDAC cases and high-risk controls. A predictive signal for PDAC was generated from a predefined cutoff established in a previous model development study. PancreaSure distinguished early-stage PDAC from controls with 76.5% sensitivity (95% CI, 67.7–83.9), significantly higher than the performance target (p = 0.005). PancreaSure achieved 87.8% specificity (95% CI, 83.9–91.4), similar to the performance goal, and significantly outperformed sensitivity of CA 19-9 alone (p = 0.02). These results confirm that PancreaSure performs well at detecting early-stage PDAC in high-risk individuals.
