Evaluating the Usefulness of the Blood Apolipoprotein A2 Isoform Index for Pancreatic Cancer Diagnosis

Background: Early detection of pancreatic cancer using existing tumor markers is challenging, and novel biomarkers are needed. Apolipoprotein A2 (APOA2), which is not directly produced by tumors, may help detect pancreatic cancer through mechanisms distinct from carbohydrate antigen 19-9 (CA 19-9). This study aimed to evaluate the diagnostic performance of the APOA2-isoform (APOA2-i) Index in patients with pancreatic cancer. Methods: Serum levels of the APOA2-i Index and CA 19-9 were measured in 76 patients with pancreatic cancer (Stage 0, n = 5; I, n = 4; II, n = 15; III, n = 19; and IV, n = 33) and 98 patients with non-pancreatic cancer (intraductal papillary mucinous neoplasm, n = 36; chronic pancreatitis, n = 33; pancreatic neuroendocrine neoplasm, n = 8; autoimmune pancreatitis, n = 9; and others, n = 12) to evaluate diagnostic performance. Results: APOA2 showed lower accuracy for advanced (stages II-IV) pancreatic cancer compared to CA 19-9 (sensitivity, 50.7% vs. 83.6%; sensitivity, 77.6% vs. 87.9%), but it provided superior accuracy for early-stage (stages 0 and I) detection (sensitivity, 33.3% vs. 22.2%; specificity, 66.7% vs. 59.4%). Three early-stage pancreatic cancer cases negative for CA 19-9 were detected with the APOA2-i Index, demonstrating high diagnostic accuracy for early-stage pancreatic cancer when both biomarkers are combined (sensitivity, 44.4%; specificity, 46.7%). The multivariate analysis revealed pancreatic cancer to be an independent risk factor for APOA2-i Index positivity (odds ratio [OR]: 3.48, p < 0.001), CA 19-9 positivity (OR: 25.5, p < 0.001), and positivity for either marker (OR: 13.3, p < 0.001). Conclusions: The APOA2-i Index, combined with CA 19-9, may improve early-stage pancreatic cancer detection, especially in challenging cases and for high-risk patient surveillance.