Up-regulation of Biglycan is Associated with Poor Prognosis and PTEN Deletion in Patients with Prostate Cancer.

Abstract

Biglycan (BGN), a proteoglycan of the extracellular matrix, is included in mRNA signatures for prostate cancer aggressiveness. To understand the impact of BGN on prognosis and its relationship to molecularly defined subsets, we analyzed BGN expression by immunohistochemistry on a tissue microarray containing 12,427 prostate cancers. Seventy-eight percent of 11,050 interpretable cancers showed BGN expression, which was considered as low intensity in 47.7% and as high intensity in 31.1% of cancers. BGN protein expression rose with increasing pathological tumor stage, Gleason grade, lymph node metastasis and early PSA recurrence (P<.0001 each). Comparison with our molecular database attached to the TMA revealed that BGN expression was linked to presence of TMPRRS2:ERG fusion and PTEN deletion (P<.0001 each). In addition, BGN was strongly linked to androgen-receptor (AR) levels (P<.0001), suggesting a hormone-depending regulation of BGN. BGN up-regulation is a frequent feature of prostate cancer that parallels tumor progression and may be useful to estimate tumor aggressiveness particularly if combined with other molecular markers.

• Authors: Frank Jacobsen, Juliane Kraft, Cornelia Schroeder, Claudia Hube-Magg, Martina Kluth, Dagmar S Lang, Ronald Simon, Guido Sauter, Jakob R Izbicki, Till S Clauditz, Andreas M Luebke, Andrea Hinsch, Waldemar Wilczak, Corinna Wittmer, Franziska Büscheck, Doris Höflmayer, Sarah Minner, Maria Christina Tsourlakis, Hartwig Huland, Markus Graefen, Lars Budäus, Imke Thederan, Georg Salomon, Thorsten Schlomm, Nathaniel Melling
• Journal: Neoplasia (New York, N.Y.) (Neoplasia) Vol. 19 Issue 9 Pg. 707-715 (Sep 2017) ISSN: 1476-5586 [Electronic] United States
• PMID: 28830008 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Biglycan
• Biomarkers, Tumor
• Oncogene Proteins, Fusion
• Receptors, Androgen
• TMPRSS2-ERG fusion protein, human
• Transcriptional Regulator ERG
• PTEN Phosphohydrolase
• PTEN protein, human
• Prostate-Specific Antigen

Topics

• Adult
• Aged
• Aged, 80 and over
• Biglycan (metabolism)
• Biomarkers, Tumor
• Cell Proliferation
• Epithelium (metabolism, pathology)
• Gene Deletion
• Humans
• Immunohistochemistry
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Neoplasm Grading
• Neoplasm Staging
• Oncogene Proteins, Fusion (genetics, metabolism)
• PTEN Phosphohydrolase (genetics)
• Phenotype
• Prognosis
• Prostate-Specific Antigen (metabolism)
• Prostatic Neoplasms (genetics, metabolism, mortality, pathology)
• Receptors, Androgen (metabolism)
• Transcriptional Regulator ERG (genetics, metabolism)