title: Plasma low-molecular-weight proteome profiling identified neuropeptide-Y as a prostate cancer biomarker polypeptide.
abstract: In prostate cancer diagnosis, PSA test has greatly contributed to the early detection of prostate cancer; however, expanding overdiagnosis and unnecessary biopsies have emerged as serious issues. To explore plasma biomarkers complementing the specificity of PSA test, we developed a unique proteomic technology QUEST-MS (Quick Enrichment of Small Targets for Mass Spectrometry). The QUEST-MS method based on 96-well formatted sequential reversed-phase chromatography allowing efficient enrichment of <20 kDa proteins quickly and reproducibly. Plasma from 24 healthy controls, 19 benign prostate hypertrophy patients, and 73 prostate cancer patients were purified with QUEST-MS and analyzed by LC/MS/MS. Among 153 057 nonredundant peptides, 189 peptides showed prostate cancer specific detection pattern, which included a neurotransmitter polypeptide neuropeptide-Y (NPY). We further validated the screening results by targeted multiple reaction monitoring technology using independent sample set (n = 110). The ROC curve analysis revealed that logistic regression-based combination of NPY, and PSA showed 81.5% sensitivity and 82.2% specificity for prostate cancer diagnosis. Thus QUEST-MS technology allowed comprehensive and high-throughput profiling of plasma polypeptides and had potential to effectively uncover very low abundant tumor-derived small molecules, such as neurotransmitters, peptide hormones, or cytokines.
authors.affiliation: Laboratory for Biomarker Development, Center for Genomic Medicine, RIKEN , General Research Building 6F, Institute of Medical Science, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Ueda
authors.forename: Ayako
authors.initials: A
authors.lastname: Tatsuguchi
authors.forename: Naomi
authors.initials: N
authors.lastname: Saichi
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Toyama
authors.forename: Kenji
authors.initials: K
authors.lastname: Tamura
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Furihata
authors.forename: Ryo
authors.initials: R
authors.lastname: Takata
authors.forename: Shusuke
authors.initials: S
authors.lastname: Akamatsu
authors.forename: Masahiro
authors.initials: M
authors.lastname: Igarashi
authors.forename: Masato
authors.initials: M
authors.lastname: Nakayama
authors.forename: Taka-Aki
authors.initials: TA
authors.lastname: Sato
authors.forename: Osamu
authors.initials: O
authors.lastname: Ogawa
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Fujioka
authors.forename: Taro
authors.initials: T
authors.lastname: Shuin
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Hidewaki
authors.initials: H
authors.lastname: Nakagawa
mesh_terms: D000368:Aged; D000595:Amino Acid Sequence; D014408:Biomarkers, Tumor / Q000737:chemistry / Q000378:metabolism*; D016022:Case-Control Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D008970:Molecular Weight; D060787:Neoplasm Grading; D009478:Neuropeptide Y / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000473:pathology; D020543:Proteome / Q000737:chemistry / Q000378:metabolism; D053719:Tandem Mass Spectrometry
chemical_list: D014408:Biomarkers, Tumor; D009478:Neuropeptide Y; D020543:Proteome