Gene expression profiling of giant cell tumor of bone reveals downregulation of extracellular matrix components decorin and lumican associated with lung metastasis

M. Lieveld, E. Bodson, G. De Boeck, B. Nouman, A. M. Cleton-Jansen, E. Korsching, M. S. Benassi, P. Picci, G. Sys, B. Poffyn, N. A. Athanasou, P. C W Hogendoorn, R. G. Forsyth

Research output: Contribution to journalArticle

Abstract

Giant cell tumor of bone (GCTB) displays worrisome clinical features such as local recurrence and occasionally metastatic disease which are unpredictable by morphology. Additional routinely usable biomarkers do not exist. Gene expression profiles of six clinically defined groups of GCTB and one group of aneurysmal bone cyst (ABC) were determined by microarray (n = 33). The most promising differentially expressed genes were validated by Q-PCR as potential biomarkers in a larger patient group (n = 41). Corresponding protein expression was confirmed by immunohistochemistry. Unsupervised hierarchical clustering reveals a metastatic GCTB cluster, a heterogeneous, non-metastatic GCTB cluster, and a primary ABC cluster. Balanced score testing indicates that lumican (LUM) and decorin (DCN) are the most promising biomarkers as they have lower level of expression in the metastatic group. Expression of dermatopontin (DPT) was significantly lower in recurrent tumors. Validation of the results was performed by paired and unpaired t test in primary GCTB and corresponding metastases, which proved that the differential expression of LUM and DCN is tumor specific rather than location specific. Our findings show that several genes related to extracellular matrix integrity (LUM, DCN, and DPT) are differentially expressed and may serve as biomarkers for metastatic and recurrent GCTB.

Original languageEnglish
Pages (from-to)703-713
Number of pages11
JournalVirchows Archiv
Volume465
Issue number6
DOIs
Publication statusPublished - Nov 27 2014

Keywords

  • Decorin
  • Extracellular matrix
  • Gene expression profiling
  • Giant cell tumor of bone
  • Osteoclastogenesis

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

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    Lieveld, M., Bodson, E., De Boeck, G., Nouman, B., Cleton-Jansen, A. M., Korsching, E., Benassi, M. S., Picci, P., Sys, G., Poffyn, B., Athanasou, N. A., Hogendoorn, P. C. W., & Forsyth, R. G. (2014). Gene expression profiling of giant cell tumor of bone reveals downregulation of extracellular matrix components decorin and lumican associated with lung metastasis. Virchows Archiv, 465(6), 703-713. https://doi.org/10.1007/s00428-014-1666-7