A High Performing Biomarker Signature for Detecting Early-Stage Pancreatic Ductal Adenocarcinoma in High-Risk Individuals

作者：Norma Alonzo Palma, Aimee L. Lucas, Bryson W. Katona, Alcibiade Athanasiou, Natasha Kureshi, Lisa Ford, Thomas Keller, Stephen G. Weber, Ralph Schiess, Thomas C. King, Diane M. Simeone, Randall E. Brand · 发表于：Cancers · 年份：2025 · DOI：10.3390/cancers17111866 · 被引用次数：8 · 研究领域：Pancreatic and Hepatic Oncology Research、Ferroptosis and cancer prognosis、Cancer Genomics and Diagnostics

Background/Objectives: Early detection of pancreatic cancer can improve patient survival, and blood-based biomarkers to aid in this are a significant need. The goal of this study was to develop and evaluate the performance of a 4- to 6-plex biomarker signature for detection of early-stage pancreatic ductal adenocarcinoma (PDAC) that performs well in high-risk controls. Methods: Enzyme-linked immunosorbent assays were used to measure 10 previously identified serum protein biomarker candidates in Stage I and II PDAC cases (n = 128), high-risk controls (n = 465), and normal-risk controls (n = 30). Various combinations of biomarker candidates (models) were trained using machine learning and tested for robustness in differentiating cases from controls on the full cohort and in clinically relevant sub-types including those with diabetes, those ≥65 years of age, and low producers of carbohydrate antigen 19-9 (CA 19-9). Results: At 98% specificity, the top performing model, which was comprised of tissue inhibitor of metalloproteinase 1 (TIMP1), intracellular adhesion molecule 1 (ICAM1), thrombospondin 1 (THBS1), cathepsin D (CTSD), and CA 19-9, achieved 85% sensitivity in the full cohort and sensitivities of 91% in diabetics, 90% in ≥65 years of age, and 60% in low CA 19-9 producers. This model demonstrated significantly higher sensitivity in detecting PDAC in the full cohort and all sub-populations compared to CA 19-9 alone (p < 0.001). Conclusions: Our findings demonstrate the f...