Expression analysis of imbalanced genes in prostate carcinoma using tissue microarrays

Br J Cancer. 2007 Jan 15;96(1):82-8. doi: 10.1038/sj.bjc.6603490. Epub 2006 Dec 5.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics
  • Fatty Acid Synthases / genetics*
  • G-Protein-Coupled Receptor Kinase 2
  • Gene Expression Profiling*
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Immunohistochemistry
  • Male
  • Multivariate Analysis
  • NM23 Nucleoside Diphosphate Kinases
  • Nucleoside-Diphosphate Kinase / genetics*
  • Phosphoprotein Phosphatases / genetics*
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • Protein Phosphatase 2
  • Proto-Oncogene Proteins c-myc / genetics*
  • Regression Analysis
  • Sensitivity and Specificity
  • Tissue Array Analysis
  • beta-Adrenergic Receptor Kinases / genetics*

Substances

  • Biomarkers, Tumor
  • NM23 Nucleoside Diphosphate Kinases
  • Proto-Oncogene Proteins c-myc
  • Fatty Acid Synthases
  • GRK2 protein, human
  • beta-Adrenergic Receptor Kinases
  • G-Protein-Coupled Receptor Kinase 2
  • NME1 protein, human
  • Nucleoside-Diphosphate Kinase
  • Phosphoprotein Phosphatases
  • Protein Phosphatase 2