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, ChangMoo Kang, Woo Jin Lee & 5 others Seungyeoun Lee, Sangjo Han, Taesung Park, Jin Young Jang, Youngsoo Kim

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 largescale samples by MRM-MS and immunoassay has clinical applicability in the early detection of PDAC.

Original languageEnglish
Pages (from-to)93117-93130
Number of pages14
JournalOncotarget
Volume8
Issue number54
DOIs
Publication statusPublished - 2017 Jan 1

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Pancreatic Neoplasms
Proteomics
Adenocarcinoma
Immunoassay
Mass Spectrometry
Pancreatic Diseases
Prealbumin
Leucine
Glycoproteins
Reference Values
Proteins
Biomarkers
Mortality
Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Park, J., Choi, Y., Namkung, J., Yi, S. G., Kim, H., Yu, J., ... Kim, Y. (2017). Diagnostic performance enhancement of pancreatic cancer using proteomic multimarker panel. Oncotarget, 8(54), 93117-93130. https://doi.org/10.18632/oncotarget.21861
Park, Jiyoung ; Choi, Yonghwan ; Namkung, Junghyun ; Yi, Sung Gon ; Kim, Hyunsoo ; Yu, Jiyoung ; Kim, Yongkang ; Kwon, Min Seok ; Kwon, Wooil ; Oh, Do Youn ; Kim, Sun Whe ; Jeong, Seung Yong ; Han, Wonshik ; Lee, Kyu Eun ; Heo, Jin Seok ; Park, Joon Oh ; Park, Joo Kyung ; Kim, Song Cheol ; Kang, ChangMoo ; Lee, Woo Jin ; Lee, Seungyeoun ; Han, Sangjo ; Park, Taesung ; Jang, Jin Young ; Kim, Youngsoo. / Diagnostic performance enhancement of pancreatic cancer using proteomic multimarker panel. In: Oncotarget. 2017 ; Vol. 8, No. 54. pp. 93117-93130.
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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 largescale samples by MRM-MS and immunoassay has clinical applicability in the early detection of PDAC.",
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Park, J, Choi, Y, Namkung, J, Yi, SG, Kim, H, Yu, J, Kim, Y, Kwon, MS, Kwon, W, Oh, DY, Kim, SW, Jeong, SY, Han, W, Lee, KE, Heo, JS, Park, JO, Park, JK, Kim, SC, Kang, C, Lee, WJ, Lee, S, Han, S, Park, T, Jang, JY & Kim, Y 2017, 'Diagnostic performance enhancement of pancreatic cancer using proteomic multimarker panel', Oncotarget, vol. 8, no. 54, pp. 93117-93130. https://doi.org/10.18632/oncotarget.21861

Diagnostic performance enhancement of pancreatic cancer using proteomic multimarker panel. / Park, Jiyoung; Choi, Yonghwan; Namkung, Junghyun; Yi, Sung Gon; Kim, Hyunsoo; Yu, Jiyoung; Kim, Yongkang; Kwon, Min Seok; Kwon, Wooil; Oh, Do Youn; Kim, Sun Whe; Jeong, Seung Yong; Han, Wonshik; Lee, Kyu Eun; Heo, Jin Seok; Park, Joon Oh; Park, Joo Kyung; Kim, Song Cheol; Kang, ChangMoo; Lee, Woo Jin; Lee, Seungyeoun; Han, Sangjo; Park, Taesung; Jang, Jin Young; Kim, Youngsoo.

In: Oncotarget, Vol. 8, No. 54, 01.01.2017, p. 93117-93130.

Research output: Contribution to journalArticle

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AU - Park, Jiyoung

AU - Choi, Yonghwan

AU - Namkung, Junghyun

AU - Yi, Sung Gon

AU - Kim, Hyunsoo

AU - Yu, Jiyoung

AU - Kim, Yongkang

AU - Kwon, Min Seok

AU - Kwon, Wooil

AU - Oh, Do Youn

AU - Kim, Sun Whe

AU - Jeong, Seung Yong

AU - Han, Wonshik

AU - Lee, Kyu Eun

AU - Heo, Jin Seok

AU - Park, Joon Oh

AU - Park, Joo Kyung

AU - Kim, Song Cheol

AU - Kang, ChangMoo

AU - Lee, Woo Jin

AU - Lee, Seungyeoun

AU - Han, Sangjo

AU - Park, Taesung

AU - Jang, Jin Young

AU - Kim, Youngsoo

PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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 largescale samples by MRM-MS and immunoassay has clinical applicability in the early detection of PDAC.

AB - 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 largescale samples by MRM-MS and immunoassay has clinical applicability in the early detection of PDAC.

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