Burgt, Yuri E. M. van der

Objectives: New methods are needed to detect pancreatic ductal adenocarcinoma (PDAC) earlier to improve outcomes. We previously reported that a panel of protein N-glycosylation traits (NGTs) discriminated PDAC from healthy controls with an area under the curve (AUC) of 0.81–0.88. However, it remained unclear whether this panel accurately differentiates PDAC from other benign pancreatic disorders. Our study aims to evaluate the performance of the NGT panel in combination with CA19-9 in a diverse cohort, including PDAC cases, healthy controls, and controls with benign pancreatic disorders. Methods: Protein N-glycosylation profiles were determined in plasma samples using an in-house developed mass spectrometry assay. CA19-9 levels were measured using a routine immunoassay test. Results of total plasma NGTs and CA19-9 were evaluated separately as well as in combination. Logistic regression was performed to calculate odds ratios (ORs), AUC, sensitivity, and specificity to determine the performance of NGTs and CA19-9 in distinguishing PDAC from controls. Results: In total, 221 individuals were included: 45 (20.4%) with PDAC, and 176 (79.6%) controls (53 healthy and 123 with benign pancreatic disease). The AUC for differentiating PDAC from the total control cohort based on the combination of the NGT panel and CA19-9 was 0.94 (95% CI, 0.90–0.97), with a sensitivity of 0.89 (95% CI, 0.78–0.98) and specificity of 0.86 (95% CI, 0.81–0.91). Comparison of PDAC cases with healthy controls only resulted in an AUC of 0.96 (95% CI, 0.93–0.99), with a sensitivity of 0.84 (95% CI, 0.73–0.93) and specificity of 0.98 (95% CI, 0.94–1.00). Conclusions: Both plasma NGTs and CA19-9 distinguish PDAC from a diverse control cohort. The accuracy further improves when these readouts are combined, showing promise for future early detection methods.