title: Discovery and Validation of Biomarkers That Distinguish Mucinous and Nonmucinous Pancreatic Cysts.
abstract: 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.
authors.affiliation: Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Jisook
authors.initials: J
authors.lastname: Park
authors.affiliation: Departments of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Hwan Sic
authors.initials: HS
authors.lastname: Yun
authors.affiliation: Departments of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Kwang Hyuck
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Departments of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Kyu Taek
authors.initials: KT
authors.lastname: Lee
authors.affiliation: Departments of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. jongk.lee@samsung.com suddenbz@skku.edu.
authors.forename: Jong Kyun
authors.initials: JK
authors.lastname: Lee
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, Seoul, South Korea. Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. jongk.lee@samsung.com suddenbz@skku.edu.
authors.forename: Soo-Youn
authors.initials: SY
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002853:Chromatography, Liquid / Q000379:methods; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010181:Pancreatic Cyst / Q000175:diagnosis / Q000378:metabolism*; D010196:Pancreatic Elastase / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D011446:Prospective Studies; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D020543:Proteome; C000617121:CELA3A protein, human; D010196:Pancreatic Elastase