Protein N-Glycosylation Traits Combined with CA19-9 Accurately Distinguish Pancreatic Cancer Cases From Healthy Controls and Benign Pancreatic Diseases

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.

Protein N-glycosylation profiles were determined in plasma samples using an in-house developed mass spectrometry assay. CA19-9 levels were measured using 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.

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).

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.