In current study, we first evaluate the clinical significance of sCD40L in PDAC patients compared with normal healthy controls and patients with chronic pancreatitis (CP, high-risk), and validate serum sCD40L as a potential biomarker for PDAC compared with pre-existing PDAC biomarkers, carbohydrate antigen 19–9 (CA19-9) and carcinoembryonic antigen (CEA) using prospectively collected human serum samples. Here, CD40LG is linked to chronic pancreatitis.