Serum carboxypeptidase A activity as a biomarker for early-stage pancreatic carcinoma

The early stage of pancreatic carcinoma lacks typical clinical signs and symptoms, and is difficult to diagnose. We developed an assay for active form of serum carboxypeptidase A (F-CPA) and its zymogen precursor pro CPA, and evaluated them as a marker for early-stage pancreatic carcinoma.

Serum CPA from 406 patients including 169 with pancreatic carcinoma, 53 with acute pancreatitis, 23 with chronic pancreatitis, and 161 with non-pancreatic diseases were assayed by a method with N-acetyl-phenylalanyl-l-3-thiaphenylalanine as substrate and dl-benzylsuccinic acid as specific inhibitor of CPA. Activation of pro CPA was carried out using trypsin.

An established assay system was performed fully automatically and possesses enough performance for routine clinical assay. This system requires 31 minutes for CPA detection. No significant differences were detected between the F-CPA activity of patients with pancreatic carcinoma and that of patients with non-pancreatic diseases (p=0.168). F-CPA was mainly increased in patients with pancreatitis. Since total-CPA (T-CPA, T-CPA=pro CPA+F-CPA) was increased both in patients with pancreatic carcinoma and those with acute pancreatitis (p<0.0001, each case), the F-CPA/T-CPA ratio was low only in the patients with pancreatic carcinoma. The rate of positivity of T-CPA in the early stage of pancreatic carcinoma in which tumor was less than 2 cm was 77%, and higher than those of CA19-9 (31%), CEA (8%), and elastase 1 (46%).

It was suggested that assays of both T-CPA and F-CPA in serum might be useful for the surveillance of early-stage pancreatic carcinoma.