Biological indicators of prognosis in Ewing's sarcoma: An emerging role for lectin galactoside-binding soluble 3 binding protein (LGALS3BP)

Diana Zambelli, Monia Zuntini, Filippo Nardi, Maria Cristina Manara, Massimo Serra, Lorena Landuzzi, Pier Luigi Lollini, Stefano Ferrari, Marco Alberghini, Antonio Llombart-Bosch, Enza Piccolo, Stefano Iacobelli, Piero Picci, Katia Scotlandi

Research output: Contribution to journalArticlepeer-review

Abstract

Starting from an experimental model that accounts for the 2 most important adverse processes to successful therapy of Ewing's sarcoma (EWS), chemoresistance and the presence of metastasis at the time of diagnosis, we defined a molecular signature of potential prognostic value. Functional annotation of differentially regulated genes revealed 3 major networks related to cell cycle, cell-to-cell interactions and cellular development. The prognostic impact of 8 genes, representative of these 3 networks, was validated in 56 EWS patients. High mRNA expression levels of HINT1, IFITM2, LGALS3BP, STOML2 and c-MYC were associated with reduced risk to death and lower risk to develop metastasis. At multivariate analysis, LGALS3BP, a matricellular protein with a role in tumor progression and metastasis, was the most important predictor of event-free survival and overall survival. The association between LGALS3BP and prognosis was confirmed at protein level, when expression of the molecule was determined in tumor tissues but not in serum, indicating a role for the protein at local tumor microenvironment. Engineered enhancement of LGALS3BP expression in EWS cells resulted in inhibition of anchorage independent cell growth and reduction of cell migration and metastasis. Silencing of LGALS3BP expression reverted cell behavior with respect to in vitro parameters, thus providing further functional validation of genetic data obtained in clinical samples. Thus, we propose LGALS3BP as a novel reliable indicator of prognosis, and we offer genetic signatures to the scientific communities for cross-validation and meta-analysis, which are indispensable tools for a rare tumor such as EWS.

Original languageEnglish
Pages (from-to)41-52
Number of pages12
JournalInternational Journal of Cancer
Volume126
Issue number1
DOIs
Publication statusPublished - Jan 1 2010

Keywords

  • Ewing's sarcoma
  • Lectin galactoside-binding soluble 3 binding protein
  • Metastasis
  • Microarray analysis
  • Prognostic markers

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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