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.
Bibliographical noteFunding Information:
This work was supported by the Collaborative Genome Program for Fostering New Post-Genome Industry(NRF-2017M3C9A5031597), a National Research Foundation grant (No. 2011-0030740), the Industrial Strategic Technology Development Program (#10079271), a grant from the Korea Health Technology R&D Project (No. HI16C2037, HI14C2640), and the SK Telecom Research Fund.
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