Park, JisookLee, EunjungPark, Kyoung-JinPark, Hyung-DooKim, Jong-WonWoo, Hye InLee, Kwang HyuckLee, Kyu-TaekLee, Jong KyunPark, Joon-OhPark, Young SukHeo, Jin SeokChoi, Seong HoChoi, Dong WookJang, Kee-TaekLee, Soo-Youn2017-11-212017Park, J., E. Lee, K. Park, H. Park, J. Kim, H. I. Woo, K. H. Lee, et al. 2017. “Large-scale clinical validation of biomarkers for pancreatic cancer using a mass spectrometry-based proteomics approach.” Oncotarget 8 (26): 42761-42771. doi:10.18632/oncotarget.17463. http://dx.doi.org/10.18632/oncotarget.17463.http://nrs.harvard.edu/urn-3:HUL.InstRepos:34375177We 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.en-USpancreatic cancerbiomarkervalidationproteomicsmass spectrometryJournal Article2017-11-2110.18632/oncotarget.17463