Clinical development of a blood biomarker using apolipoprotein-A2 isoforms for early detection of pancreatic cancer.

IF 6.9 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Journal of Gastroenterology Pub Date : 2024-03-01 Epub Date: 2024-01-23 DOI:10.1007/s00535-023-02072-w

Ayumi Kashiro, Michimoto Kobayashi, Takanori Oh, Mitsuko Miyamoto, Jun Atsumi, Kengo Nagashima, Keiko Takeuchi, Satoshi Nara, Susumu Hijioka, Chigusa Morizane, Shojiro Kikuchi, Shingo Kato, Ken Kato, Hiroki Ochiai, Daisuke Obata, Yuya Shizume, Hiroshi Konishi, Yumiko Nomura, Kotone Matsuyama, Cassie Xie, Christin Wong, Ying Huang, Giman Jung, Sudhir Srivastava, Hiromu Kutsumi, Kazufumi Honda

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引用次数: 0

Abstract

Background: We have previously reported apolipoprotein A2-isoforms (apoA2-is) as candidate plasma biomarkers for early-stage pancreatic cancer. The aim of this study was the clinical development of apoA2-is.

Methods: We established a new enzyme-linked immunosorbent sandwich assay for apoA2-is under the Japanese medical device Quality Management System requirements and performed in vitro diagnostic tests with prespecified end points using 2732 plasma samples. The clinical equivalence and significance of apoA2-is were compared with CA19-9.

Results: The point estimate of the area under the curve to distinguish between pancreatic cancer (n = 106) and healthy controls (n = 106) 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 end point. The cutoff apoA2-ATQ/AT of 59.5 μg/mL was defined based on a specificity of 95% in 2000 healthy samples, and the reliability of specificities was confirmed in two independent healthy cohorts as 95.3% (n = 106, 95% CI 89.4-98.0%) and 95.8% (n = 400, 95% CI 93.3-97.3%). The sensitivities of apoA2-ATQ/AT for detecting both stage I (47.4%) and I/II (50%) pancreatic cancers were higher than those of CA19-9 (36.8% and 46.7%, respectively). The combination of apoA2-ATQ/AT (cutoff, 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. The clinical performance of apoA2-is was blindly confirmed by the National Cancer Institute Early Detection Research Network.

Conclusions: The clinical performance of ApoA2-ATQ/AT as a blood biomarker is equivalent to or better than that of CA19-9.

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利用载脂蛋白-A2 同工酶进行血液生物标记的临床开发，用于早期检测胰腺癌。

背景：我们曾报道过载脂蛋白A2-异构体（apoA2-is）是早期胰腺癌的候选血浆生物标志物。本研究的目的是对载脂蛋白 A2-is进行临床开发：我们根据日本医疗器械质量管理体系的要求建立了一种新型酶联免疫吸附夹心法检测载脂蛋白A2-is，并使用2732份血浆样本进行了预设终点的体外诊断测试。将载脂蛋白A2-is与CA19-9的临床等效性和显著性进行了比较：结果：载脂蛋白A2-ATQ/AT区分胰腺癌（n = 106）和健康对照组（n = 106）的曲线下面积的点估计值[0.879，95% 置信区间（CI）：0.832-0.925]高于CA19-9（0.849，95% CI 0.793-0.905），达到了主要终点。根据 2000 份健康样本中 95% 的特异性定义了 59.5 μg/mL 的载脂蛋白A2-ATQ/AT 临界值，特异性的可靠性在两个独立的健康队列中得到了证实，分别为 95.3% （n = 106，95% CI 89.4-98.0%）和 95.8%（n = 400，95% CI 93.3-97.3%）。载脂蛋白A2-ATQ/AT检测I期（47.4%）和I/II期（50%）胰腺癌的灵敏度均高于CA19-9（分别为36.8%和46.7%）。结合使用载脂蛋白A2-ATQ/AT（临界值为59.5 μg/mL）和CA19-9（37 U/mL）可将胰腺癌的灵敏度提高到87.7%，而单独使用CA19-9的灵敏度仅为69.8%。美国国家癌症研究所早期检测研究网络对载脂蛋白A2-is的临床表现进行了盲法确认：结论：载脂蛋白A2-ATQ/AT作为血液生物标记物的临床性能等同于或优于CA19-9。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Gastroenterology 医学-胃肠肝病学

CiteScore

12.20

自引率

1.60%

发文量

审稿时长

4-8 weeks

期刊介绍： The Journal of Gastroenterology, which is the official publication of the Japanese Society of Gastroenterology, publishes Original Articles (Alimentary Tract/Liver, Pancreas, and Biliary Tract), Review Articles, Letters to the Editors and other articles on all aspects of the field of gastroenterology. Significant contributions relating to basic research, theory, and practice are welcomed. These publications are designed to disseminate knowledge in this field to a worldwide audience, and accordingly, its editorial board has an international membership.