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

Apolipoprotein A2-isoform Blood biomarker Carbohydrate antigen 19-9 (CA19-9) Early detection of pancreatic cancer

Journal

Journal of gastroenterology
ISSN: 1435-5922
Titre abrégé: J Gastroenterol
Pays: Japan
ID NLM: 9430794

Informations de publication

Date de publication:
23 Jan 2024
Historique:
received: 10 07 2023
accepted: 26 12 2023
medline: 23 1 2024
pubmed: 23 1 2024
entrez: 23 1 2024
Statut: aheadofprint

Résumé

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

Sections du résumé

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

Identifiants

DOI: 10.1007/s00535-023-02072-w PMID: 38261000
pubmed: 38261000
doi: 10.1007/s00535-023-02072-w
pii: 10.1007/s00535-023-02072-w
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Japan
ID : AMED P-CREATE [No. 21cm0106403h0006]
Organisme : Japan
ID : AMED P-PROMOTE No. 22ama221401h0001

Informations de copyright

© 2024. The Author(s).

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Auteurs

Ayumi Kashiro (A)

Department of Bioregulation, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-Ku, Tokyo, 113-8602, Japan.
Institute for Advanced Medical Sciences, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-Ku, Tokyo, 113-8602, Japan.

Michimoto Kobayashi (M)

Toray Industries, Inc., 2-1-1 Muromachi Nihonbashi, Chuo-Ku, Tokyo, 103-8666, Japan.

Takanori Oh (T)

Toray Industries, Inc., 2-1-1 Muromachi Nihonbashi, Chuo-Ku, Tokyo, 103-8666, Japan.

Mitsuko Miyamoto (M)

Toray Industries, Inc., 2-1-1 Muromachi Nihonbashi, Chuo-Ku, Tokyo, 103-8666, Japan.

Jun Atsumi (J)

Toray Industries, Inc., 2-1-1 Muromachi Nihonbashi, Chuo-Ku, Tokyo, 103-8666, Japan.

Kengo Nagashima (K)

Keio University Hospital, 35 Shinanomachi, Shinjuku-Ku, Tokyo, 160-8582, Japan.

Keiko Takeuchi (K)

Institute for Advanced Medical Sciences, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-Ku, Tokyo, 113-8602, Japan.

Satoshi Nara (S)

Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan.

Susumu Hijioka (S)

Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan.

Chigusa Morizane (C)

Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan.

Shojiro Kikuchi (S)

Institute of Advanced Medical Sciences, Hyogo Medical University, 1-1 Mukogawa, Nishinomiya, Hyogo, 663-8501, Japan.

Shingo Kato (S)

Department of Clinical Cancer Genomics, Yokohama City University Hospital, 3-9 Fukuura, Kanazawa-Ku, Yokohama, Kanagawa, 236-0004, Japan.

Ken Kato (K)

Department of Head and Neck Esophageal Medical Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan.

Hiroki Ochiai (H)

Department of Gastroenterological Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan.

Daisuke Obata (D)

Center for Clinical Research and Advanced Medicine, Shiga University of Medical Science, Tsukiwamachi Seta, Otsu, Shiga, 520-2192, Japan.

Yuya Shizume (Y)

Toray Industries, Inc., 2-1-1 Muromachi Nihonbashi, Chuo-Ku, Tokyo, 103-8666, Japan.

Hiroshi Konishi (H)

Japan Cancer Society, 5-3-3 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan.

Yumiko Nomura (Y)

Japan Cancer Society, 5-3-3 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan.

Kotone Matsuyama (K)

Department of Health Policy and Management, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-Ku, Tokyo, 113-8602, Japan.

Cassie Xie (C)

Biostatistics, Bioinformatics and Epidemiology Program, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109-1024, USA.

Christin Wong (C)

Bio Tool Department (Toray Molecular Oncology Lab.), Toray International America Inc., Brisbane, CA, 94005, USA.

Ying Huang (Y)

Biostatistics, Bioinformatics and Epidemiology Program, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109-1024, USA.

Giman Jung (G)

Bio Tool Department (Toray Molecular Oncology Lab.), Toray International America Inc., Brisbane, CA, 94005, USA.

Sudhir Srivastava (S)

Division of Cancer Prevention, National Cancer Institute, Rockville, MD, 20850, USA.
National Cancer Institute Early Detection Research Network, Rockville, MD, 20850, USA.

Hiromu Kutsumi (H)

Center for Clinical Research and Advanced Medicine, Shiga University of Medical Science, Tsukiwamachi Seta, Otsu, Shiga, 520-2192, Japan.

Kazufumi Honda (K)

Department of Bioregulation, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-Ku, Tokyo, 113-8602, Japan. k-honda@nms.ac.jp.
Institute for Advanced Medical Sciences, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-Ku, Tokyo, 113-8602, Japan. k-honda@nms.ac.jp.

Classifications MeSH