title: Biomarker Development for Intraductal Papillary Mucinous Neoplasms Using Multiple Reaction Monitoring Mass Spectrometry.
abstract: Intraductal papillary mucinous neoplasm (IPMN) is a common precursor of pancreatic cancer (PC). Much clinical attention has been directed toward IPMNs due to the increase in the prevalence of PC. The diagnosis of IPMN depends primarily on a radiological examination, but the diagnostic accuracy of this tool is not satisfactory, necessitating the development of accurate diagnostic biomarkers for IPMN to prevent PC. Recently, high-throughput targeted proteomic quantification methods have accelerated the discovery of biomarkers, rendering them powerful platforms for the evolution of IPMN diagnostic biomarkers. In this study, a robust multiple reaction monitoring (MRM) pipeline was applied to discovery and verify IPMN biomarker candidates in a large cohort of plasma samples. Through highly reproducible MRM assays and a stringent statistical analysis, 11 proteins were selected as IPMN marker candidates with high confidence in 184 plasma samples, comprising a training (n = 84) and test set (n = 100). To improve the discriminatory power, we constructed a six-protein panel by combining marker candidates. The multimarker panel had high discriminatory power in distinguishing between IPMN and controls, including other benign diseases. Consequently, the diagnostic accuracy of IPMN can be improved dramatically with this novel plasma-based panel in combination with a radiological examination.
authors.affiliation: Department of Biomedical Engineering, ‡Surgery and Cancer Research Institute, and §Department of Pathology, Seoul National University College of Medicine , 28 Yongon-Dong, Seoul 110-799 Korea.|Department of Statistics and ⊥Interdisciplinary Program in Bioinformatics, Seoul National University , Daehak-dong, Seoul 151-742, Korea.
authors.forename: Yikwon
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Biomedical Engineering, ‡Surgery and Cancer Research Institute, and §Department of Pathology, Seoul National University College of Medicine , 28 Yongon-Dong, Seoul 110-799 Korea.|Department of Statistics and ⊥Interdisciplinary Program in Bioinformatics, Seoul National University , Daehak-dong, Seoul 151-742, Korea.
authors.forename: MeeJoo
authors.initials: M
authors.lastname: Kang
authors.affiliation: Department of Biomedical Engineering, ‡Surgery and Cancer Research Institute, and §Department of Pathology, Seoul National University College of Medicine , 28 Yongon-Dong, Seoul 110-799 Korea.|Department of Statistics and ⊥Interdisciplinary Program in Bioinformatics, Seoul National University , Daehak-dong, Seoul 151-742, Korea.
authors.forename: Dohyun
authors.initials: D
authors.lastname: Han
authors.affiliation: Department of Biomedical Engineering, ‡Surgery and Cancer Research Institute, and §Department of Pathology, Seoul National University College of Medicine , 28 Yongon-Dong, Seoul 110-799 Korea.|Department of Statistics and ⊥Interdisciplinary Program in Bioinformatics, Seoul National University , Daehak-dong, Seoul 151-742, Korea.
authors.forename: Hyunsoo
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Biomedical Engineering, ‡Surgery and Cancer Research Institute, and §Department of Pathology, Seoul National University College of Medicine , 28 Yongon-Dong, Seoul 110-799 Korea.|Department of Statistics and ⊥Interdisciplinary Program in Bioinformatics, Seoul National University , Daehak-dong, Seoul 151-742, Korea.
authors.forename: KyoungBun
authors.initials: K
authors.lastname: Lee
authors.affiliation: Department of Biomedical Engineering, ‡Surgery and Cancer Research Institute, and §Department of Pathology, Seoul National University College of Medicine , 28 Yongon-Dong, Seoul 110-799 Korea.|Department of Statistics and ⊥Interdisciplinary Program in Bioinformatics, Seoul National University , Daehak-dong, Seoul 151-742, Korea.
authors.forename: Sun-Whe
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Department of Biomedical Engineering, ‡Surgery and Cancer Research Institute, and §Department of Pathology, Seoul National University College of Medicine , 28 Yongon-Dong, Seoul 110-799 Korea.|Department of Statistics and ⊥Interdisciplinary Program in Bioinformatics, Seoul National University , Daehak-dong, Seoul 151-742, Korea.
authors.forename: Yongkang
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Biomedical Engineering, ‡Surgery and Cancer Research Institute, and §Department of Pathology, Seoul National University College of Medicine , 28 Yongon-Dong, Seoul 110-799 Korea.|Department of Statistics and ⊥Interdisciplinary Program in Bioinformatics, Seoul National University , Daehak-dong, Seoul 151-742, Korea.
authors.forename: Taesung
authors.initials: T
authors.lastname: Park
authors.affiliation: Department of Biomedical Engineering, ‡Surgery and Cancer Research Institute, and §Department of Pathology, Seoul National University College of Medicine , 28 Yongon-Dong, Seoul 110-799 Korea.|Department of Statistics and ⊥Interdisciplinary Program in Bioinformatics, Seoul National University , Daehak-dong, Seoul 151-742, Korea.
authors.forename: Jin-Young
authors.initials: JY
authors.lastname: Jang
authors.affiliation: Department of Biomedical Engineering, ‡Surgery and Cancer Research Institute, and §Department of Pathology, Seoul National University College of Medicine , 28 Yongon-Dong, Seoul 110-799 Korea.|Department of Statistics and ⊥Interdisciplinary Program in Bioinformatics, Seoul National University , Daehak-dong, Seoul 151-742, Korea.
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood / Q000302:isolation & purification*; D001798:Blood Proteins / Q000302:isolation & purification*; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018297:Neoplasms, Cystic, Mucinous, and Serous / Q000097:blood* / Q000175:diagnosis; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000175:diagnosis; D012372:ROC Curve
chemical_list: D014408:Biomarkers, Tumor; D001798:Blood Proteins
keywords: IPMN; LC−MRM; biomarker development; plasma; targeted proteomics