TMPRSS2-ERG expression predicts prostate cancer survival and associates with stromal biomarkers

PLoS One. 2014 Feb 5;9(2):e86824. doi: 10.1371/journal.pone.0086824. eCollection 2014.

Abstract

The TMPRSS2-ERG gene fusion is found in approximately half of all prostate cancers. The functional and prognostic significance of TMPRSS2-ERG is, however, not fully understood. Based on a historical watchful waiting cohort, an association between TMPRSS2-ERG, evaluated as positive immune staining, and shorter survival of prostate cancer patients was identified. Expression of ERG was also associated with clinical markers such as advanced tumor stage, high Gleason score, presence of metastasis and prognostic tumor cell markers such as high Ki67, pEGFR and pAkt. Novel associations between TMPRSS2-ERG and alterations in the tumor stroma, for example, increased vascular density, hyaluronan and PDGFRβ and decreased Caveolin-1, all known to be associated with an aggressive disease, were found. The present study suggests that the TMPRSS2-ERG fusion gene is associated with a more aggressive prostate cancer phenotype, supported by changes in the tumor stroma.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Caveolin 1 / biosynthesis
  • Disease-Free Survival
  • Early Growth Response Protein 1 / biosynthesis*
  • ErbB Receptors / biosynthesis
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Ki-67 Antigen / biosynthesis
  • Male
  • Oncogene Proteins, Fusion / biosynthesis*
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / mortality*
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / therapy
  • Proto-Oncogene Proteins c-akt / biosynthesis
  • Serine Endopeptidases / biosynthesis*
  • Survival Rate

Substances

  • CAV1 protein, human
  • Caveolin 1
  • EGR1 protein, human
  • Early Growth Response Protein 1
  • Ki-67 Antigen
  • Oncogene Proteins, Fusion
  • EGFR protein, human
  • ErbB Receptors
  • Proto-Oncogene Proteins c-akt
  • Serine Endopeptidases
  • TMPRSS2 protein, human

Grant support

The Swedish Research Council and the Swedish Cancer Society supported the work. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.