Thrombospondin-2 as a diagnostic biomarker for distal cholangiocarcinoma and pancreatic ductal adenocarcinoma

Purpose: Distal cholangiocarcinoma and pancreatic ductal adenocarcinoma are malignancies with poor prognoses that can be difficult to distinguish preoperatively. Thrombospondin-2 has been proposed as a novel diagnostic biomarker for early pancreatic ductal adenocarcinoma. The aim of the present study was to evaluate thrombospondin-2 as a diagnostic and prognostic biomarker in combination with current biomarker CA 19-9 for distal cholangiocarcinoma and pancreatic ductal adenocarcinoma. Methods: Thrombospondin-2 was measured in prospectively collected serum samples from patients who underwent surgery with a histopathological diagnosis of distal cholangiocarcinoma (N = 51), pancreatic ductal adenocarcinoma (N = 52) and benign pancreatic diseases (N = 27) as well as healthy blood donors (N = 52) using an enzyme-linked immunosorbent assay. Results: Thrombospondin-2 levels (ng/ml) were similar in distal cholangiocarcinoma 55 (41–77) and pancreatic ductal adenocarcinoma 48 (35–80) (P = 0.221). Thrombospondin-2 + CA 19-9 had an area under the curve of 0.92 (95% CI 0.88–0.97) in differentiating distal cholangiocarcinoma and pancreatic ductal adenocarcinoma from healthy donors which was superior to CA 19-9 alone (P < 0.001). The diagnostic value of adding thrombospondin-2 to CA 19-9 was larger in early disease stages. Thrombospondin-2 did not provide additional value to CA 19-9 in differentiating the benign disease group; however, heterogeneity was notable in the benign cohort. Three of five patients with autoimmune pancreatitis patients had greatly elevated thrombospondin-2 levels. Thrombospondin-2 levels had no correlation with prognoses. Conclusions: Serum thrombospondin-2 in combination with CA 19-9 has potential as a biomarker for distal cholangiocarcinoma and pancreatic cancer