title: Identification and validation of potential new biomarkers for prostate cancer diagnosis and prognosis using 2D-DIGE and MS.
abstract: This study was designed to identify and validate potential new biomarkers for prostate cancer and to distinguish patients with and without biochemical relapse. Prostate tissue samples analyzed by 2D-DIGE (two-dimensional difference in gel electrophoresis) and mass spectrometry (MS) revealed downregulation of secernin-1 (P<0.044) in prostate cancer, while vinculin showed significant upregulation (P<0.001). Secernin-1 overexpression in prostate tissue was validated using Western blot and immunohistochemistry while vinculin expression was validated using immunohistochemistry. These findings indicate that secernin-1 and vinculin are potential new tissue biomarkers for prostate cancer diagnosis and prognosis, respectively. For validation, protein levels in urine were also examined by Western blot analysis. Urinary vinculin levels in prostate cancer patients were significantly higher than in urine from nontumor patients (P=0.006). Using multiple reaction monitoring-MS (MRM-MS) analysis, prostatic acid phosphatase (PAP) showed significant higher levels in the urine of prostate cancer patients compared to controls (P=0.012), while galectin-3 showed significant lower levels in the urine of prostate cancer patients with biochemical relapse, compared to those without relapse (P=0.017). Three proteins were successfully differentiated between patients with and without prostate cancer and patients with and without relapse by using MRM. Thus, this technique shows promise for implementation as a noninvasive clinical diagnostic technique.
authors: Institute of Pathology, RWTH Aachen University, 52074 Aachen, Germany.
authors: Cordelia
authors: C
authors: Geisler
authors: Institute of Pathology, RWTH Aachen University, 52074 Aachen, Germany.
authors: Nadine T
authors: NT
authors: Gaisa
authors: Department of Urology, RWTH Aachen University, 52074 Aachen, Germany.
authors: David
authors: D
authors: Pfister
authors: Department of Urology, University Hospital Carl Gustav Carus, 01307 Dresden, Germany.
authors: Susanne
authors: S
authors: Fuessel
authors: Institute of Pathology, University Hospital Bonn (UKB), 53127 Bonn, Germany.
authors: Glen
authors: G
authors: Kristiansen
authors: Institute of Pathology, RWTH Aachen University, 52074 Aachen, Germany.
authors: Till
authors: T
authors: Braunschweig
authors: Institute of Pathology, RWTH Aachen University, 52074 Aachen, Germany.
authors: Sonja
authors: S
authors: Gostek
authors: Medizinisches Proteom-Center, Ruhr-University Bochum, 44801 Bochum, Germany ; Leibniz-Institut für Analytische Wissenschaften ISAS e.V., 44139 Dortmund, Germany.
authors: Birte
authors: B
authors: Beine
authors: Medizinisches Proteom-Center, Ruhr-University Bochum, 44801 Bochum, Germany.
authors: Hanna C
authors: HC
authors: Diehl
authors: University of Victoria-Genome British Columbia Proteomics Centre, University of Victoria, Victoria, BC, Canada V8Z 7X8.
authors: Angela M
authors: AM
authors: Jackson
authors: University of Victoria-Genome British Columbia Proteomics Centre, University of Victoria, Victoria, BC, Canada V8Z 7X8 ; Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC, Canada V8W 2Y2.
authors: Christoph H
authors: CH
authors: Borchers
authors: Department of Urology, RWTH Aachen University, 52074 Aachen, Germany.
authors: Axel
authors: A
authors: Heidenreich
authors: Medizinisches Proteom-Center, Ruhr-University Bochum, 44801 Bochum, Germany ; Leibniz-Institut für Analytische Wissenschaften ISAS e.V., 44139 Dortmund, Germany.
authors: Helmut E
authors: HE
authors: Meyer
authors: Institute of Pathology, RWTH Aachen University, 52074 Aachen, Germany.
authors: Ruth
authors: R
authors: Knüchel
authors: Institute of Pathology, RWTH Aachen University, 52074 Aachen, Germany ; Medizinisches Proteom-Center, Ruhr-University Bochum, 44801 Bochum, Germany ; Leibniz-Institut für Analytische Wissenschaften ISAS e.V., 44139 Dortmund, Germany.
authors: Corinna
authors: C
authors: Henkel
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis* / Q000652:urine; D006801:Humans; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D025202:Molecular Diagnostic Techniques; D009419:Nerve Tissue Proteins / Q000032:analysis; D011379:Prognosis; D011467:Prostate / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000175:diagnosis*; D046888:Tissue Array Analysis; D057825:Two-Dimensional Difference Gel Electrophoresis / Q000379:methods*; D016596:Vinculin / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; D009419:Nerve Tissue Proteins; C471696:SCRN1 protein, human; C488955:VCL protein, human; D016596:Vinculin