title: Diagnostic potential in bladder cancer of a panel of tumor markers (calreticulin, gamma -synuclein, and catechol-o-methyltransferase) identified by proteomic analysis.
abstract: Using proteomic analysis, we previously identified calreticulin (CRT) as a potentially useful urinary marker for bladder cancer. Now, we have also identified gamma -synuclein (SNCG) and a soluble isoform of catechol-o-methyltransferase (s-COMT) as novel candidates for tumor markers in bladder cancer, by means of proteomic analysis. In the process of establishing a superior tumor marker system, we investigated the diagnostic value of a combination assay of these three proteins. Voided urine samples were obtained from 112 bladder cancer and 230 control patients. Urinary CRT, SNCG, and s-COMT were measured as a combined marker by quantitative western blot analysis. Relative concentration of each protein was calculated and the diagnostic value of a concomitant examination of these markers was evaluated by receiver operator characteristic analysis. With the best diagnostic cutoff, the overall sensitivity of the combined markers was 76.8% (95% confidence interval, 69-81%) with a specificity of 77.4% (72-80%), while those of a single use of CRT were 71.4% and 77.8%, respectively. When evaluated in relation to tumor characteristics, such as grade, stage, size, and outcome of urinary cytology, the diagnostic capacity of the combined markers was equal to or better than that of CRT in all categories. Concomitant use of CRT, SNCG, and s-COMT had higher sensitivity for detection of bladder cancer than did single use of CRT. Our study suggests that use of this panel of markers will improve the diagnosis of bladder cancer and may allow the development of a protein microarray assay or multi-channel enzyme-linked immunosorbent assay.
authors.affiliation: Department of Urology, Shiga University of Medical Science, Shiga 520-2192, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Iwaki
authors.forename: Susumu
authors.initials: S
authors.lastname: Kageyama
authors.forename: Takahiro
authors.initials: T
authors.lastname: Isono
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Wakabayashi
authors.forename: Yusaku
authors.initials: Y
authors.lastname: Okada
authors.forename: Koji
authors.initials: K
authors.lastname: Yoshimura
authors.forename: Akito
authors.initials: A
authors.lastname: Terai
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Arai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iwamura
authors.forename: Mutsushi
authors.initials: M
authors.lastname: Kawakita
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Yoshiki
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000652:urine*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000175:diagnosis / Q000652:urine; D037282:Calreticulin / Q000652:urine*; D002292:Carcinoma, Renal Cell / Q000175:diagnosis / Q000652:urine; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000652:urine*; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000652:urine; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009419:Nerve Tissue Proteins / Q000652:urine*; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000652:urine; D040901:Proteomics; D012680:Sensitivity and Specificity; D051843:Synucleins; D001743:Urinary Bladder / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000652:urine; D051845:gamma-Synuclein
chemical_list: D014408:Biomarkers, Tumor; D037282:Calreticulin; D009419:Nerve Tissue Proteins; D051843:Synucleins; D051845:gamma-Synuclein; D002394:Catechol O-Methyltransferase