1. Plasma low-molecular-weight proteome profiling identified neuropeptide-Y as a prostate cancer biomarker polypeptide.
- Author
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Ueda K, Tatsuguchi A, Saichi N, Toyama A, Tamura K, Furihata M, Takata R, Akamatsu S, Igarashi M, Nakayama M, Sato TA, Ogawa O, Fujioka T, Shuin T, Nakamura Y, and Nakagawa H
- Subjects
- Aged, Amino Acid Sequence, Biomarkers, Tumor chemistry, Case-Control Studies, Humans, Male, Middle Aged, Molecular Sequence Data, Molecular Weight, Neoplasm Grading, Prostatic Neoplasms pathology, Proteome chemistry, Proteome metabolism, Tandem Mass Spectrometry, Biomarkers, Tumor metabolism, Neuropeptide Y blood, Prostatic Neoplasms blood
- 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.
- Published
- 2013
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