Macrophage inhibitory cytokine 1, syncollin and thrombospondin-2 in pancreatic ductal adenocarcinoma and chronic pancreatitis differentiation.

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with a rising global incidence. Differentiating PDAC from non-malignant pancreatic conditions, particularly chronic pancreatitis (CP), remains challenging due to overlapping clinical and radiological features, highlighting the need for new biomarkers. The best-validated serum biomarker, carbohydrate antigen 19-9 (CA19-9), has limited clinical utility due to its suboptimal sensitivity and specificity. This study aimed to evaluate the diagnostic performance of serum macrophage inhibitory cytokine 1 (GDF15), syncollin (SYCN), and thrombospondin-2 (TSP-2), both alone and in multi-marker panels, for differentiating PDAC from CP and healthy controls (HCs). The selection of these markers was based on prior evidence linking GDF15 to PDAC diagnosis and prognosis, SYCN to pancreatic tissue damage, and TSP-2 to tumor microenvironment remodeling. Methods: This study included 188 individuals: 78 diagnosed with PDAC, 79 with CP and 31 HCs. PDAC and CP were diagnosed based on clinical, imaging, histopathological, and laboratory findings, and classified according to the 8th TNM classification and the updated Cambridge system, respectively. Serum GDF15, SYCN, and TSP-2 levels were quantified using ELISA. Statistical analyses included group comparisons, correlation testing, and receiver operating characteristic (ROC) curve analysis with assessment of the area under the curve (AUC). Results: GDF15 and SYCN were significantly elevated in PDAC compared with both CP and HCs, whereas TSP-2 did not differ significantly between those groups. For PDAC vs HCs, GDF15 provided the strongest overall discrimination (AUC = 0.86; sensitivity 97%, specificity 71%), while SYCN showed a lower AUC (0.77) but very high specificity (94%). The combined GDF15 + SYCN panel increased AUC to 0.89. For PDAC vs CP, GDF15 achieved moderate diagnostic performance (AUC = 0.73), SYCN performed less well (AUC = 0.65), and TSP-2 performed near chance (AUC = 0.52). Incorporating age and bilirubin in the model improved discrimination between PDAC and CP, yielding a maximum AUC of 0.88. Additionally, positive correlations were observed between SYCN and diabetes, as well as between GDF15 and hyperbilirubinemia, in patients with PDAC. Conclusions: These results suggest that GDF15 and SYCN are promising serum biomarkers for PDAC, whereas TSP-2 appears to have limited diagnostic utility.