Quantitative analysis of BTF3, HINT1, NDRG1 and ODC1 protein over-expression in human prostate cancer tissue

PLoS One. 2013 Dec 27;8(12):e84295. doi: 10.1371/journal.pone.0084295. eCollection 2013.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / metabolism
  • Carcinogenesis
  • Cell Cycle Proteins / metabolism*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Male
  • Middle Aged
  • Nerve Tissue Proteins / metabolism*
  • Nuclear Proteins / metabolism*
  • Ornithine Decarboxylase / metabolism*
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology*
  • Transcription Factors / metabolism*

Substances

  • Biomarkers, Tumor
  • Cell Cycle Proteins
  • HINT1 protein, human
  • Intracellular Signaling Peptides and Proteins
  • N-myc downstream-regulated gene 1 protein
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Transcription Factors
  • transcription factor BTF3
  • Ornithine Decarboxylase

Grants and funding

This research was funded by the Prostate Cancer Research Centre charity and St Peter’s Trust. The authors are grateful to Mike Millar, Sheila MacPherson and Nancy Evans of Edinburgh University for help with staining and to Daniel Ciantar, UCL for Huygens software use. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.