The use of advanced imaging technologies for the identification of
pancreatic cysts has become widespread. However, accurate differential diagnosis between mucinous
cysts (MC) and nonmucinous
cysts (NMC) consisting of pseudocysts (NMC1) and nonmucinous neoplastic
cysts (NMC2) remains a challenge. Thus, it is necessary to develop novel
biomarkers for the differential diagnosis of
pancreatic cysts. An integrated proteomics approach yielded differentially expressed
proteins in MC that were verified subsequently in 99
pancreatic cysts (21 NMC1, 41 NMC2, and 37 MC) using a method termed GeLC-stable
isotope dilution-multiple reaction monitoring-mass spectrometry (GeLC-
SID-MRM-MS) along with established immunoassay techniques. We identified 223
proteins by nanoscale liquid chromatography coupled to tandem mass spectrometry (nano LC/MS-MS). Nine candidate
biomarkers were identified, including
polymeric immunoglobulin receptor (PIGR),
lipocalin 2 (LCN2),
Fc fragment of
IgG-
binding protein (FCGBP), lithostathine-1-alpha (REG1A), afamin (AFM),
chymotrypsin C (
caldecrin; CTRC),
amylase, alpha 2B (pancreatic; AMY2B),
lectin, galactoside-binding, soluble, 3
binding protein (LGALS3BP), and
chymotrypsin-like
elastase family, member 3A (CELA3A), which were established as
biomarker candidates for MC. In particular, we have shown that a
biomarker subset, including AFM, REG1A, PIGR, and LCN2, could differentiate MC not only from NMC (including NMC1) but also from NMC2. Overall, the MS-based comprehensive proteomics approach used in this study established a novel set of candidate
biomarkers that address a gap in efforts to distinguish early pancreatic lesions at a time when more successful therapeutic interventions may be possible.