Oncotarget

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This article has been corrected. Correction in: Oncotarget. 2018; 9:5514.

Diagnostic performance enhancement of pancreatic cancer using proteomic multimarker panel

Jiyoung Park, Yonghwan Choi, Junghyun Namkung, Sung Gon Yi, Hyunsoo Kim, Jiyoung Yu, Yongkang Kim, Min-Seok Kwon, Wooil Kwon, Do-Youn Oh, Sun-Whe Kim, Seung-Yong Jeong, Wonshik Han, Kyu Eun Lee, Jin Seok Heo, Joon Oh Park, Joo Kyung Park, Song Cheol Kim, Chang Moo Kang, Woo Jin Lee, Seungyeoun Lee, Sangjo Han, Taesung Park _, Jin-Young Jang and Youngsoo Kim

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Oncotarget. 2017; 8:93117-93130. https://doi.org/10.18632/oncotarget.21861

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Abstract

Jiyoung Park1,2,*, Yonghwan Choi3,14,*, Junghyun Namkung3, Sung Gon Yi3, Hyunsoo Kim1,2, Jiyoung Yu1,2, Yongkang Kim4, Min-Seok Kwon4, Wooil Kwon5, Do-Youn Oh6, Sun-Whe Kim5, Seung-Yong Jeong5, Wonshik Han5, Kyu Eun Lee5, Jin Seok Heo7, Joon Oh Park8, Joo Kyung Park9, Song Cheol Kim10, Chang Moo Kang11, Woo Jin Lee12, Seungyeoun Lee13, Sangjo Han3, Taesung Park4, Jin-Young Jang5 and Youngsoo Kim1,2

1Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea

2Department of Biomedical Engineering, Seoul National University College of Medicine, Seoul, Korea

3Immunodiagnostics R&D Team, IVD Business Unit 5, SK Telecom, Seoul, Korea

4Department of Statistics, Seoul National University, Seoul, Korea

5Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea

6Department of Internal Medicine and Cancer Research Institute, Seoul National University Hospital, Seoul, Korea

7Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

8Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

9Department of Internal Medicine, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Korea

10Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea

11Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea

12Center for Liver Cancer, National Cancer Center, Seoul, Korea

13Department of Mathematics and Statistics, Sejong University, Seoul, Korea

14School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology (POSTECH), Pohang, Korea

*The authors have contributed equally to this work

Correspondence to:

Taesung Park, email: [email protected]

Jin-Young Jang, email: [email protected]

Youngsoo Kim, email: [email protected]

Keywords: pancreatic cancer, proteomics, diagnostic biomarker, multimarker panel, multiple reaction monitoring

Received: July 10, 2017     Accepted: August 29, 2017     Published: October 16, 2017

ABSTRACT

Due to its high mortality rate and asymptomatic nature, early detection rates of pancreatic ductal adenocarcinoma (PDAC) remain poor.

We measured 1000 biomarker candidates in 134 clinical plasma samples by multiple reaction monitoring-mass spectrometry (MRM-MS). Differentially abundant proteins were assembled into a multimarker panel from a training set (n=684) and validated in independent set (n=318) from five centers. The level of panel proteins was also confirmed by immunoassays. The panel including leucine-rich alpha-2 glycoprotein (LRG1), transthyretin (TTR), and CA19-9 had a sensitivity of 82.5% and a specificity of 92.1%. The triple-marker panel exceeded the diagnostic performance of CA19-9 by more than 10% (AUCCA19-9 = 0.826, AUCpanel= 0.931, P < 0.01) in all PDAC samples and by more than 30% (AUCCA19-9 = 0.520, AUCpanel = 0.830, P < 0.001) in patients with normal range of CA19-9 (<37U/mL). Further, it differentiated PDAC from benign pancreatic disease (AUCCA19-9 = 0.812, AUCpanel = 0.892, P < 0.01) and other cancers (AUCCA19-9 = 0.796, AUCpanel = 0.899, P < 0.001).

Overall, the multimarker panel that we have developed and validated in large-scale samples by MRM-MS and immunoassay has clinical applicability in the early detection of PDAC.


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