Validation of a Serum-Based Biomarker Signature for Detection of Early-Stage Pancreatic Ductal Adenocarcinoma
Aimee L. Lucas, Diane M. Simeone, Bryson W. Katona, Salvatore Paiella, George Zogopoulos, Rosalie C. Sears, Eli Marie Grindedal, Raymond Wadlow, Erkut Borazanci, Ora Gordon, Fay Kastrinos, José G. Treviño, Sonia S. Kupfer, Walter G. Park, Jessica N. Everett, Natasha Kureshi, George R. DeMuth, Lisa Ford, Thomas C. King, Norma Alonzo Palma, Randall E. Brand
Abstract
BACKGROUND & AIMS: This study's goal was to clinically validate the performance of PancreaSure (Immunovia, Inc), a serum biomarker signature composed of tissue inhibitor of metalloproteinase 1, intercellular adhesion molecule 1, cathepsin D, thrombospondin 1, and carbohydrate antigen 19-9 for detection of early-stage pancreatic ductal adenocarcinoma (PDAC) in an independent cohort. METHODS: Signature analytes were retrospectively measured in serum samples from a blinded cohort of stage I and stage II PDAC cases and genetic and/or familial high-risk controls. A predictive signal for PDAC was generated from a predefined cutoff established in a previous model development study optimized at 98% specificity. Diagnostic sensitivity and specificity were evaluated on the full cohort. McNemar or 2-proportion z tests were used to compare test performance between stage I and stage II cases, and between controls with and without a germline mutation and/or familial susceptibility to PDAC. Diagnostic certainty of test results was evaluated using a Monte Carlo simulation. RESULTS: PancreaSure distinguished early-stage PDAC (n = 202) from high-risk controls (n = 864) with 78.5% sensitivity (95% CI, 72.5%-83.9%) and 93.5% specificity (95% CI, 91.9%-95.2%), significantly outperforming carbohydrate antigen 19-9 alone (P < .001). The test performed consistently between stage I and II PDAC and between controls with and without genetic or familial susceptibility. In addition, 93.7% of all samples were classified as PDAC-positive or PDAC-negative with 100% certainty. Only 1.8% of all samples were classified with <80% certainty. CONCLUSIONS: These findings indicate that PancreaSure is a high-performing biomarker test to aid in the detection of early-stage PDAC. Overall, this work represents an important step toward improving early-stage diagnostic success.