Prospective Study Using Plasma Apolipoprotein A2-Isoforms to Screen for High-Risk Status of Pancreatic Cancer

SIMPLE SUMMARY: Apolipoprotein A2 isoforms (apoA2-i) have been identified as minimally invasive biomarkers for detecting pancreatic cancer (PC) and high-risk individuals for PC. We investigated the efficiency of an enrichment strategy for high-risk individuals using a combination of blood testing for apoA2-i with imaging examinations in the general population. We enrolled 5120 subjects in experimental pancreatic cancer screening, with 84 subjects (1.3%) showing abnormal results for apoA2-i. Pancreatic diseases were recognized in about 30% of subjects with an apoA2-ATQ/AT level of ≤35 μg/mL. Among them, 1 pancreatic cancer and 15 high-risk individuals with intraductal papillary mucinous neoplasm were detected. ApoA2-i has the potential to enrich PC and high-risk status by increasing the diagnostic probability before imaging examinations. ABSTRACT: Apolipoprotein A2-ATQ/AT (apoA2-ATQ/AT) has been identified as a minimally invasive biomarker for detecting pancreatic cancer (PC) and high-risk (HR) individuals for PC. To establish an efficient enrichment strategy for HR, we carried out a plasma apoA2-ATQ/AT level-based prospective screening study among the general population. The subjects for the screening study were recruited at six medical check-up facilities in Japan between October 2015 and January 2017. We evaluated the positive predictive value (PPV) of the plasma apoA2-ATQ/AT level of ≤35 μg/mL for detecting PC and HR. Furthermore, we prospectively confirmed its diagnostic accuracy with another post-diagnosis population in a cross-sectional study. We enrolled 5120 subjects in experimental screening, with 84 subjects (1.3%) showing positive results for apoA2-ATQ/AT. Pancreatic abnormalities were recognized in 26 of the 84 subjects from imaging examinations. Pancreatic abnormalities detected included 1 PC and 15 HR abnormalities, such as cystic lesions including intraductal papillary mucinous neoplasm. The PPV of apoA2-ATQ/AT for detecting PC and HR was 33.3%. Moreover, a combination study with another cross-sectional study revealed that the area under the curve for apoA2-ATQ/AT to distinguish PC from healthy controls was 0.903. ApoA2-ATQ/AT has the potential to enrich PC and HR by increasing the diagnostic probability before imaging examinations.