A Biomarker Panel for the Detection of Pancreatic Cancer

Background: Pancreatic cancer is an aggressive malignancy with poor survival. Most patients are diagnosed at advanced or metastatic stages because early disease is often asymptomatic and effective screening tools are lacking. We evaluated a three-marker model comprising serum CA19-9 in combination with the plasma proteins ITIH3 and CEACAM1 for pancreatic ductal adenocarcinoma (PDAC) detection. Methods: Matched plasma and serum samples were collected from 649 participants (250 PDAC cases and 399 controls). Plasma proteins were enriched using high-surface area magnetic covalent organic framework (COF) polymers. Serum CA19-9 was measured using the Tosoh Bioscience immunoassay. The marker panel was trained using a radial-based SVM with repeated 10-fold cross-validation using a set-aside training sample set. The derived model along with a fixed cutoff corresponding to 95% sensitivity in training samples were independently validated using a blinded sample set. Results: In the independent blinded validation, the combined panel of serum CA19-9 with plasma ITIH3 and CEACAM1 achieved an AUC of 0.917 indicating that the three-marker panel maintained strong performance in distinguishing PDAC from controls. At the prefixed threshold, the three-marker panel had a specificity of 53.3% (95% CI: 46.8-59.7%), significantly outperforming CA19-9 alone at 14.5% (95% CI: 10.4-19.7%). Conclusions: In independently blinded validation, combining plasma ITIH3 and CEACAM1 with serum CA19-9 substantially improved diagnostic performance for PDAC, achieving high specificity while maintaining 95% sensitivity compared with serum CA19-9 alone. These findings support further validation of this three-marker panel as a potential PDAC monitoring and detection approach in larger, multicenter studies.