Oncotarget

Research Papers:

Large-scale clinical validation of biomarkers for pancreatic cancer using a mass spectrometry-based proteomics approach

Jisook Park, Eunjung Lee, Kyoung-Jin Park, Hyung-Doo Park, Jong-Won Kim, Hye In Woo, Kwang Hyuck Lee, Kyu-Taek Lee, Jong Kyun Lee, Joon-Oh Park, Young Suk Park, Jin Seok Heo, Seong Ho Choi, Dong Wook Choi, Kee-Taek Jang and Soo-Youn Lee _

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Oncotarget. 2017; 8:42761-42771. https://doi.org/10.18632/oncotarget.17463

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Abstract

Jisook Park1, Eunjung Lee2, Kyoung-Jin Park3, Hyung-Doo Park3, Jong-Won Kim3, Hye In Woo4, Kwang Hyuck Lee5, Kyu-Taek Lee5, Jong Kyun Lee5, Joon-Oh Park6, Young Suk Park6, Jin Seok Heo7, Seong Ho Choi7, Dong Wook Choi7, Kee-Taek Jang8 and Soo-Youn Lee3,9

1Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

2Division of Genetics and Genomics, Boston Children's Hospital and Harvard Medical School, Boston, MA, United States

3Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

4Department of Laboratory Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea

5Division of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

6Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

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

8Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

9Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

Correspondence to:

Soo-Youn Lee, email: suddenbz@skku.edu

Keywords: pancreatic cancer, biomarker, validation, proteomics, mass spectrometry

Received: October 06, 2016     Accepted: April 15, 2017     Published: April 27, 2017

ABSTRACT

We performed an integrated analysis of proteomic and transcriptomic datasets to develop potential diagnostic markers for early pancreatic cancer. In the discovery phase, a multiple reaction monitoring assay of 90 proteins identified by either gene expression analysis or global serum proteome profiling was established and applied to 182 clinical specimens. Nine proteins (P < 0.05) were selected for the independent validation phase and quantified using stable isotope dilution-multiple reaction monitoring-mass spectrometry in 456 specimens. Of these proteins, four proteins (apolipoprotein A-IV, apolipoprotein CIII, insulin-like growth factor binding protein 2 and tissue inhibitor of metalloproteinase 1) were significantly altered in pancreatic cancer in both the discovery and validation phase (P < 0.01). Moreover, a panel including carbohydrate antigen 19-9, apolipoprotein A-IV and tissue inhibitor of metalloproteinase 1 showed better performance for distinguishing early pancreatic cancer from pancreatitis (Area under the curve = 0.934, 86% sensitivity at fixed 90% specificity) than carbohydrate antigen 19-9 alone (71% sensitivity).

Overall, we present the panel of robust biomarkers for early pancreatic cancer diagnosis through bioinformatics analysis that combined transcriptomic and proteomic data as well as rigorous validation on a large number of independent clinical samples.


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