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Precision Medicine and Imaging

Development and Multiple Validation of the Protein Multi-marker Panel for Diagnosis of Pancreatic Cancer

Yoseop Kim, Injoon Yeo, Iksoo Huh, Jaenyeon Kim, Dohyun Han, Jin-Young Jang and Youngsoo Kim
Yoseop Kim
1Interdisciplinary Program in Bioengineering, Seoul National University, College of Engineering, Seoul, Republic of South Korea.
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Injoon Yeo
2Institute of Medical and Biological Engineering, Medical Research Center, Seoul National University College of Medicine, Seoul, Republic of South Korea.
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  • ORCID record for Injoon Yeo
Iksoo Huh
3College of Nursing and Research Institute of Nursing Science, Seoul National University, Seoul, Republic of South Korea.
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  • ORCID record for Iksoo Huh
Jaenyeon Kim
1Interdisciplinary Program in Bioengineering, Seoul National University, College of Engineering, Seoul, Republic of South Korea.
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Dohyun Han
4Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of South Korea.
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Jin-Young Jang
5Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of South Korea.
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  • For correspondence: biolab@snu.ac.kr jangjy4@snu.ac.kr
Youngsoo Kim
1Interdisciplinary Program in Bioengineering, Seoul National University, College of Engineering, Seoul, Republic of South Korea.
2Institute of Medical and Biological Engineering, Medical Research Center, Seoul National University College of Medicine, Seoul, Republic of South Korea.
6Institute of Bioengineering, Seoul National University, Seoul, Republic of South Korea.
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  • For correspondence: biolab@snu.ac.kr jangjy4@snu.ac.kr
DOI: 10.1158/1078-0432.CCR-20-3929 Published April 2021
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Abstract

Purpose: To develop and validate a protein-based, multi-marker panel that provides superior pancreatic ductal adenocarcinoma (PDAC) detection abilities with sufficient diagnostic performance.

Experimental Design: A total of 959 plasma samples from patients at multiple medical centers were used. To construct an optimal, diagnostic, multi-marker panel, we applied data preprocessing procedure to biomarker candidates. The multi-marker panel was developed using a training set comprised of 261 PDAC cases and 290 controls. Subsequent evaluations were performed in a validation set comprised of 65 PDAC cases and 72 controls. Further validation was performed in an independent set comprised of 75 PDAC cases and 47 controls.

Results: A multi-marker panel containing 14 proteins was developed. The multi-marker panel achieved AUCs of 0.977 and 0.953 for the training set and validation set, respectively. In an independent validation set, the multi-marker panel yielded an AUC of 0.928. The diagnostic performance of the multi-marker panel showed significant improvements compared with carbohydrate antigen (CA) 19-9 alone (training set AUC = 0.977 vs. 0.872, P < 0.001; validation set AUC = 0.953 vs. 0.832, P < 0.01; independent validation set AUC = 0.928 vs. 0.771, P < 0.001). When the multi-marker panel and CA 19-9 were combined, the diagnostic performance of the combined panel was improved for all sets.

Conclusions: This multi-marker panel and the combined panel showed statistically significant improvements in diagnostic performance compared with CA 19-9 alone and has the potential to complement CA 19-9 as a diagnostic marker in clinical practice.

Footnotes

  • Note: Supplementary data for this article are available at Clinical Cancer Research Online (http://clincancerres.aacrjournals.org/).

  • Clin Cancer Res 2021;27:2236–45

  • Received October 5, 2020.
  • Revision received December 22, 2020.
  • Accepted January 21, 2021.
  • Published first January 27, 2021.
  • ©2021 American Association for Cancer Research.
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Clinical Cancer Research: 27 (8)
April 2021
Volume 27, Issue 8
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Development and Multiple Validation of the Protein Multi-marker Panel for Diagnosis of Pancreatic Cancer
Yoseop Kim, Injoon Yeo, Iksoo Huh, Jaenyeon Kim, Dohyun Han, Jin-Young Jang and Youngsoo Kim
Clin Cancer Res April 15 2021 (27) (8) 2236-2245; DOI: 10.1158/1078-0432.CCR-20-3929

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Development and Multiple Validation of the Protein Multi-marker Panel for Diagnosis of Pancreatic Cancer
Yoseop Kim, Injoon Yeo, Iksoo Huh, Jaenyeon Kim, Dohyun Han, Jin-Young Jang and Youngsoo Kim
Clin Cancer Res April 15 2021 (27) (8) 2236-2245; DOI: 10.1158/1078-0432.CCR-20-3929
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