Diagnostic performance enhancement of pancreatic cancer using proteomic multimarker panel

作者：Park Jiyoung; Choi Yonghwan; Namkung Junghyun; Yi Sung Gon; Kim Hyunsoo; Yu Jiyoung; Kim Yongkang; Kwon Min Seok; Kwon Wooil; Oh Do Youn; Kim Sun Whe; Jeong Seung Yong; Han Wonshik; Lee Kyu Eun; Heo Jin Seok; Park Joon Oh; Park Joo Kyung; Kim Song Cheol; Kang Chang Moo; Lee Woo Jin; Lee Seungyeoun; Han Sangjo; Park Taesung; Jang Jin Young; Kim Youngsoo

来源：Oncotarget, 2017, 8(54): 93117-93130.

DOI：10.18632/oncotarget.21861

• pancreatic cancer
• proteomics
• diagnostic biomarker
• multimarker panel
• multiple reaction monitoring

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% (AUC(CA19-9) = 0.826, AUC(panel) = 0.931, P < 0.01) in all PDAC samples and by more than 30% (AUC(CA19-9) = 0.520, AUC(panel) = 0.830, P < 0.001) in patients with normal range of CA19-9 (< 37U/mL). Further, it differentiated PDAC from benign pancreatic disease (AUC(CA19-9) = 0.812, AUC(panel) = 0.892, P < 0.01) and other cancers (AUC(CA19-9) = 0.796, AUC(panel) = 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.

• 出版日期2017-11-3