Expression analysis of imbalanced genes in prostate carcinoma using tissue microarrays.
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.
Prowatke
I
I
Division of Molecular Genetics, German Cancer Research Center, Heidelberg, Germany.
Devens
F
F
Benner
A
A
Gröne
E F
EF
Mertens
D
D
Gröne
H-J
HJ
Lichter
P
P
Joos
S
S
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*
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