title: Expression analysis of imbalanced genes in prostate carcinoma using tissue microarrays.
abstract: To identify candidate genes relevant for prostate tumour prognosis and progression, we performed an exhaustive gene search in seven previously described genomic-profiling studies of 161 prostate tumours, and four expression profiling studies of 61 tumours. From the resulting list of candidate genes, six were selected for protein-expression analysis based on the availability of antibodies applicable to paraffinised tissue: fatty acid synthase (FASN), MYC, beta-adrenergic receptor kinase 1 (BARK1, GRK2) the catalytic subunits of protein phosphatases PP1alpha (PPP1CA) and PP2A (PPP2CB) and metastasis suppressor NM23-H1. These candidates were analysed by immunohistochemistry (IHC) on a tissue microarray containing 651 cores of primary prostate cancer samples and benign prostatic hyperplasias (BPH) from 175 patients. In univariate analysis, expression of PP1alpha (P=0.001) was found to strongly correlate with Gleason score. MYC immunostaining negatively correlated with both pT-stage and Gleason score (P<0.001 each) in univariate as well as in multivariate analysis. Furthermore, a subgroup of patients with high Gleason scores was characterised by a complete loss of BARK1 protein (P=0.023). In conclusion, our study revealed novel molecular markers of potential diagnostic and therapeutic relevance for prostate carcinoma.
authors.affiliation: Division of Molecular Genetics, German Cancer Research Center, Heidelberg, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Prowatke
authors.forename: F
authors.initials: F
authors.lastname: Devens
authors.forename: A
authors.initials: A
authors.lastname: Benner
authors.forename: E F
authors.initials: EF
authors.lastname: Gröne
authors.forename: D
authors.initials: D
authors.lastname: Mertens
authors.forename: H-J
authors.initials: HJ
authors.lastname: Gröne
authors.forename: P
authors.initials: P
authors.lastname: Lichter
authors.forename: S
authors.initials: S
authors.lastname: Joos
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D064429:Fatty Acid Synthases / Q000235:genetics*; D054769:G-Protein-Coupled Receptor Kinase 2; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D015999:Multivariate Analysis; D054778:NM23 Nucleoside Diphosphate Kinases; D009701:Nucleoside-Diphosphate Kinase / Q000235:genetics*; D010749:Phosphoprotein Phosphatases / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D054648:Protein Phosphatase 2; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D012044:Regression Analysis; D012680:Sensitivity and Specificity; D046888:Tissue Array Analysis; D051552:beta-Adrenergic Receptor Kinases / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D054778:NM23 Nucleoside Diphosphate Kinases; D016271:Proto-Oncogene Proteins c-myc; D064429:Fatty Acid Synthases; C496567:GRK2 protein, human; D051552:beta-Adrenergic Receptor Kinases; D054769:G-Protein-Coupled Receptor Kinase 2; C517938:NME1 protein, human; D009701:Nucleoside-Diphosphate Kinase; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2