Dataset Information

QUEST-MS for plasma biomarkers complementing the specificity of PSA test

ABSTRACT: 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. The LC/MS/MS data from 24 healthy controls, 19 benign prostate hypertrophy (BPH) patients, and 73 prostate cancer patients plasma were subjected to label-free quantification analysis on Expressionist proteome server. Data processing: Mascot Server 2.3.1 was used with the database SwissProt 2011_08 (531473 sequences,188463640 residues). Enzyme: semiTrypsin. Search parameters: Peptide Mass Tolerance : +- 3 ppm, Fragment Mass Tolerance:+-0.8 Da. Fixed modifications:Carbamidomethyl (C). Variable modifications:Oxidation (M),Deamidated (NQ). Max Missed Cleavages:2.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Plasma

SUBMITTER: Koji Ueda

LAB HEAD: Koji Ueda

PROVIDER: PXD000383 | Pride | 2014-01-28

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	110801_110530_ProstateLMW_BPH_384_8.raw	Raw
	110801_110530_ProstateLMW_BPH_417_7.raw	Raw
	110801_110530_ProstateLMW_BPH_97_2.raw	Raw
	110801_110530_ProstateLMW_GS6_48_6.raw	Raw
	110801_110530_ProstateLMW_GS6_576_5.raw	Raw

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Publications

Plasma low-molecular-weight proteome profiling identified neuropeptide-Y as a prostate cancer biomarker polypeptide.

Ueda Koji K Tatsuguchi Ayako A Saichi Naomi N Toyama Atsuhiko A Tamura Kenji K Furihata Mutsuo M Takata Ryo R Akamatsu Shusuke S Igarashi Masahiro M Nakayama Masato M Sato Taka-Aki TA Ogawa Osamu O Fujioka Tomoaki T Shuin Taro T Nakamura Yusuke Y Nakagawa Hidewaki H

Journal of proteome research 20130911 10

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 ...[more]

PMID: 23991666

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Project description:BACKGROUND: Noninvasive methods for the early identify diagnosis of prostatitis, benign prostatic hyperplasia (BPH), and prostate cancer (PCa) are current clinical challenges.METHODS: The serum metabolites of 20 healthy individuals and patients with prostatitis, BPH, or PCa were identified using untargeted liquid chromatography-mass spectrometry (LC-MS).RESULTS: Organic acid metabolites had good sensitivity and specificity in differentiating prostatitis, BPH, and PCa. In addition, targeted LC-MS was used to verify the organic acid metabolites in the serum of a validation cohort. Three diagnostic models identified patients with PROSTATITIS: phenyllactic acid (area under the curve [AUC]=0.773), pyroglutamic acid (AUC=0.725), and pantothenic acid (AUC=0.721). Three diagnostic models identified BPH: citric acid (AUC=0.859), malic acid (AUC=0.820), and D-glucuronic acid (AUC=0.810). Four diagnostic models identified PCa: 3-hydroxy-3-methylglutaric acid (AUC=0.804), citric acid (AUC=0.918), malic acid (AUC=0.862), and phenyllactic acid (AUC=0.713). Two diagnostic models distinguished BPH from PCa: phenyllactic acid (AUC=0.769) and pyroglutamic acid (AUC=0.761). Three diagnostic models distinguished benign BPH from PROSTATITIS: citric acid (AUC=0.842), ethylmalonic acid (AUC=0.814), and hippuric acid (AUC=0.733). Six diagnostic models distinguished BPH from prostatitis: citric acid (AUC=0.926), pyroglutamic acid (AUC=0.864), phenyllactic acid (AUC=0.850), ethylmalonic acid (AUC=0.843), 3-hydroxy-3-methylglutaric acid (AUC=0.817), and hippuric acid (AUC=0.791). Three diagnostic models distinguished PCa patients with PROSTATITISA < 4.0 ng/mL from those with PSA > 4.0 ng/mL: 5-hydromethyl-2-furoic acid (AUC=0.749), ethylmalonic acid (A UC=0.750), and pyroglutamic acid (AUC=0.929).CONCLUSIONS: These results suggest that serum organic acid metabolites can be used as biomarkers to differentiate prostatitis, BPH, and PCa. Untargeted assay is reported in the current study MTBLS6039.Targeted organic acid assay is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS6038' rel='noopener noreferrer' target='_blank'>MTBLS6038</a>.

Project description:BACKGROUND: Noninvasive methods for the early identify diagnosis of prostatitis, benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are current clinical challenges.METHODS: The serum metabolites of 20 healthy individuals and patients with prostatitis, BPH, or PCa were identified using untargeted liquid chromatography-mass spectrometry (LC-MS).RESULTS: Organic acid metabolites had good sensitivity and specificity in differentiating prostatitis, BPH, and PCa. In addition, targeted LC-MS was used to verify the organic acid metabolites in the serum of a validation cohort. Three diagnostic models identified patients with PROSTATITIS: phenyllactic acid (area under the curve [AUC]=0.773), pyroglutamic acid (AUC=0.725), and pantothenic acid (AUC=0.721). Three diagnostic models identified BPH: citric acid (AUC=0.859), malic acid (AUC=0.820), and D[1]glucuronic acid (AUC=0.810). Four diagnostic models identified PCa: 3-hydroxy-3-methylglutaric acid (AUC=0.804), citric acid (AUC=0.918), malic acid (AUC=0.862), and phenyllactic acid (AUC=0.713). Two diagnostic models distinguished BPH from PCa: phenyllactic acid (AUC=0.769) and pyroglutamic acid (AUC=0.761). Three diagnostic models distinguished benign BPH from PROSTATITIS: citric acid (AUC=0.842), ethylmalonic acid (AUC=0.814), and hippuric acid (AUC=0.733). Six diagnostic models distinguished BPH from prostatitis: citric acid (AUC=0.926), pyroglutamic acid (AUC=0.864), phenyllactic acid (AUC=0.850), ethylmalonic acid (AUC=0.843), 3-hydroxy- 3-methylglutaric acid (AUC=0.817), and hippuric acid (AUC=0.791). Three diagnostic models distinguished PCa patients with PROSTATITISA < 4.0 ng/mL from those with PSA > 4.0 ng/mL: 5-hydromethyl-2-furoic acid (AUC=0.749), ethylmalonic acid (A UC=0.750), and pyroglutamic acid (AUC=0.929).CONCLUSIONS: These results suggest that serum organic acid metabolites can be used as biomarkers to differentiate prostatitis, BPH, and PCa. Targeted organic acid assay is reported in the current study MTBLS6038.Untargeted assay is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS6039' rel='noopener noreferrer' target='_blank'>MTBLS6039</a>.