Abstract B007: Early detection and risk stratification of pancreatic cancer using apolipoprotein A2-isoforms as a blood biomarker

Abstract

Abstract To reduce the mortality rate of pancreatic cancer, there is an urgent need to develop a biomarker that can efficiently screen for pancreatic cancer in blood tests. We had identified the unique processing of C-terminal amino acids of apolipoprotein A2 homodimers, we named it apolipoprotein A2-isoforms (apoA2-i). ApoA2-i consists of three isoforms with different C-terminal amino acids. Especially, we had reported that apoA2-ATQ/AT, known as the intermediate isoform, was significantly reduced in the bloodstream of pancreatic adenocarcinoma (PDAC) patients compared to healthy controls. However, previous reports were investigated using a research use only (RUO) reagent, which could not be used in clinical settings. We generated a novel ELISA for measuring apoA2-i under the Japanese medical device Quality Management System requirements, and measured the concentration of apoA2-i in 2,732 of plasma samples. The clinical equivariance and significance of apoA2i were evaluated by pre-specified endpoints. The point estimate of the area under the curve to distinguish between PDAC and healthy controls was higher for apoA2-ATQ/AT [0.879, 95% confidence interval (CI): 0.832–0.925] than for CA19-9 (0.849, 95%CI: 0.793–0.905) and achieved the primary endpoint. The cut-off apoA2-ATQ/AT of 59.5 μg/mL was defined based on 95% specificity in 2,000 healthy samples. The sensitivity of apoA2-ATQ/AT for detecting both stage I (47.4%) and I/II (50%) of PDAC was higher than that of CA19-9 (36.8% and 46.7%, respectively). The combination of apoA2-ATQ/AT (cut-off, 59.5 μg/mL) and CA19-9 (37 U/mL) increased the sensitivity for pancreatic cancer to 87.7% compared with 69.8% for CA19-9 alone. ApoA2-ATQ/AT has equivalent or better clinical performance to CA19-9 as a blood biomarker. Citation Format: Kazufumi Honda, Ayumi H. Kashiro, Michimoto Kobayashi, Keiko Takeuchi, Yuya Shizume, Takanori Oh, Chigusa Morizane, Susumu Hijioka, Satoshi Nara. Early detection and risk stratification of pancreatic cancer using apolipoprotein A2-isoforms as a blood biomarker [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr B007.