Plasma Protein Biomarkers for Early Detection of Pancreatic Cancer

Early detection of pancreatic cancer remains challenging, and reliable circulating biomarkers are needed to enable earlier diagnosis and improve clinical outcomes. We conducted a plasma proteomics study using the Olink Explore HT platform to identify novel biomarker candidates for early-stage pancreatic cancer. The study included 42 patients with stage I-II pancreatic cancer and 43 matched controls. Plasma protein levels were quantified using the Olink Proximity Extension Assay, and differential abundance was assessed using Welch's t-test with correction for multiple testing. Diagnostic performance was evaluated using the area under the receiver operating characteristic curve (AUC). Among 5419 proteins analyzed, 982 showed significant differences between cases and controls. Carboxylesterase 3 (CES3) was the most significantly decreased protein, whereas leukocyte immunoglobulin-like receptor B4 (LILRB4) was the most significantly increased protein; both demonstrated excellent diagnostic performance (AUC = 0.91). In addition, pancreatic polypeptide (PPY) showed markedly reduced levels in patients with tumors arising in the head of the pancreas, suggesting anatomical specificity. This comprehensive Olink-based proteomic analysis identifies CES3 and LILRB4 as promising plasma biomarkers for early-stage pancreatic cancer and highlights PPY as informative for tumor localization. These findings provide a valuable resource for biomarker discovery and support further validation of these candidates for noninvasive early detection and risk stratification.