Abstract
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.
Highlights
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal gastrointestinal malignancies and the seventh leading cause of cancer-related deaths
The study participants were recruited from 5 major medical centers in Seoul, Korea: National Cancer Center (NCC), Seoul National University Hospital or Seoul National University Hospital Healthcare System Gangnam Center (SNUH), Samsung Medical Center (SMC), Asan Medical Center (AMC), and Yonsei Severance Hospital (YSH)
For the cross-platform validation studies, 1008 plasma samples, including those that were used in the verification step [PDAC =401, normal control (NL) =349, other cancer (OC) =149, pancreatic benign (PB) =109], were collected between January 2011 and December 2013
Summary
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal gastrointestinal malignancies and the seventh leading cause of cancer-related deaths. Most pancreatic cancer (PC) patients die within 1 year after the initial diagnosis, and approximately 7% survives over 5 years. The absence of symptoms in its initial stages and insufficient early detection tools lead to poor prognoses, and roughly 80% of the disease is unresectable at the time of diagnosis [1]. The close evaluation is limited to symptomatic or recurrent cancer patients in addition to lack of cost-effective, specific, and reliable screening tests [2]. Current diagnostic tools (e.g., imaging, biopsy) are likely to be expensive, time-consuming, and invasive. There is an unmet need for a clinical examination method that can discriminate malignancy from normal and benign states
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