Serum diagnostic markers of early-stage pancreatic ductal adenocarcinoma (PDAC) are needed, especially for Stage I disease. As tumors grow and cause pancreatic atrophy, markers derived from pancreatic parenchyma such as serum carboxypeptidase A activity (CPA) lose diagnostic performance. We evaluated, with CA19-9, serum CPA as a marker of early pancreatic cancer.
Serum CPA activity levels were measured in 345 controls undergoing pancreatic surveillance, divided into two sets, set one being used to establish a reference range. Variants within the CPA1 locus were sought for their association with pancreatic CPA1 expression to determine if such variants associated with serum CPA levels. 190 patients with resectable PDAC were evaluated.
Among controls, those having one or more minor alleles of CPA1 variants rs6955723 or rs2284682 had significantly higher serum CPA levels than those without (P=0.001). None of the PDAC cases with pancreatic atrophy had an elevated CPA. Among 122 PDAC cases without atrophy: Defining serum CPA diagnostic cut-offs by a subject’s CPA1 variants, yielded a diagnostic sensitivity of 18% at 99% specificity (95% confidence interval; 11.7, 26)(vs. 11.1% sensitivity using a uniform diagnostic cut-off); combining CPA with variant-stratified CA19-9 yielded a sensitivity of 68.0% (59.0, 76.2) vs. 63.1% (53.9, 71.7) for CA19-9 alone; among Stage I PDAC cases, diagnostic sensitivity was 51.9% (31.9, 71.3), vs. 37.0% (19.4, 57.6) for CA19-9 alone. In the validation control set, the variant-stratified diagnostic cut-off yielded a specificity of 98.2%.
Serum CPA activity has diagnostic utility before the emergence of pancreatic atrophy as a marker of localized PDAC, including Stage I disease.

Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.