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

Citation:

Park J, Lee E, Park K-J, Park H-D, Kim J-W, Woo HI, Lee KH, Lee K-T, Lee JK, Park J-O, Park YS, Heo JS, Choi SH, Choi DW, Jang K-T, Lee S-Y. Large-scale clinical validation of biomarkers for pancreatic cancer using a mass spectrometry-based proteomics approach. Oncotarget 2017;8(26):42761-42771.

Date Published:

2017 Jun 27

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.

Last updated on 11/28/2017