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

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2024年1月23日

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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

摘要

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.