Diagnostic performance enhancement of pancreatic cancer using proteomic multimarker panel
Authors
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 ; Chang Moo Kang ; Woo Jin Lee ; Seungyeoun Lee ; Sangjo Han ; Taesung Park ; Jin-Young Jang ; Youngsoo Kim
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 large-scale samples by MRM-MS and immunoassay has clinical applicability in the early detection of PDAC.