title: Quantitative analysis of BTF3, HINT1, NDRG1 and ODC1 protein over-expression in human prostate cancer tissue.
abstract: Prostate carcinoma is the most common cancer in men with few, quantifiable, biomarkers. Prostate cancer biomarker discovery has been hampered due to subjective analysis of protein expression in tissue sections. An unbiased, quantitative immunohistochemical approach provided here, for the diagnosis and stratification of prostate cancer could overcome this problem. Antibodies against four proteins BTF3, HINT1, NDRG1 and ODC1 were used in a prostate tissue array (> 500 individual tissue cores from 82 patients, 41 case pairs matched with one patient in each pair had biochemical recurrence). Protein expression, quantified in an unbiased manner using an automated analysis protocol in ImageJ software, was increased in malignant vs non-malignant prostate (by 2-2.5 fold, p<0.0001). Operating characteristics indicate sensitivity in the range of 0.68 to 0.74; combination of markers in a logistic regression model demonstrates further improvement in diagnostic power. Triple-labeled immunofluorescence (BTF3, HINT1 and NDRG1) in tissue array showed a significant (p<0.02) change in co-localization coefficients for BTF3 and NDRG1 co-expression in biochemical relapse vs non-relapse cancer epithelium. BTF3, HINT1, NDRG1 and ODC1 could be developed as epithelial specific biomarkers for tissue based diagnosis and stratification of prostate cancer.
authors.affiliation: Prostate Cancer Research Centre, Division of Surgery, University College London, London, United Kingdom.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Symes
authors.affiliation: Prostate Cancer Research Centre, Division of Surgery, University College London, London, United Kingdom.
authors.forename: Marte
authors.initials: M
authors.lastname: Eilertsen
authors.affiliation: The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Michael
authors.initials: M
authors.lastname: Millar
authors.affiliation: Prostate Cancer Research Centre, Division of Surgery, University College London, London, United Kingdom.
authors.forename: Joseph
authors.initials: J
authors.lastname: Nariculam
authors.affiliation: Department of Histopathology, University College London Hospital, London, United Kingdom.
authors.forename: Alex
authors.initials: A
authors.lastname: Freeman
authors.affiliation: Prostate Cancer Research Centre, Division of Surgery, University College London, London, United Kingdom.
authors.forename: Maria
authors.initials: M
authors.lastname: Notara
authors.affiliation: Prostate Cancer Research Centre, Division of Surgery, University College London, London, United Kingdom.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Feneley
authors.forename: Hitendra R H
authors.initials: HR
authors.lastname: Patel
authors.affiliation: Division of Surgery, Oncology, Urology and Women's Health, University Hospital of Northern Norway, Tromso, Norway.
authors.forename: Hitenedra R H
authors.initials: HR
authors.lastname: Patel
authors.affiliation: Prostate Cancer Research Centre, Division of Surgery, University College London, London, United Kingdom.
authors.forename: John R W
authors.initials: JR
authors.lastname: Masters
authors.affiliation: Prostate Cancer Research Centre, Division of Surgery, University College London, London, United Kingdom.
authors.forename: Aamir
authors.initials: A
authors.lastname: Ahmed
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D063646:Carcinogenesis; D018797:Cell Cycle Proteins / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D014157:Transcription Factors / Q000378:metabolism*; D000099259:N-myc Downstream-Regulated Gene 1 Protein
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D009955:Ornithine Decarboxylase; D014157:Transcription Factors; D000099259:N-myc Downstream-Regulated Gene 1 Protein; C063306:HINT1 protein, human; C063552:transcription factor BTF3