Insulin-like growth factor II mRNA-binding protein 3 expression predicts unfavorable prognosis in patients with neuroblastoma

Cancer Sci. 2011 Dec;102(12):2191-8. doi: 10.1111/j.1349-7006.2011.02100.x. Epub 2011 Oct 17.

Abstract

Insulin-like growth factor II mRNA-binding protein 3 (IMP3) has been reported to enhance proliferation and invasion in various cancers. The role of IMP3 on neuroblastoma (NB) is unknown. We aimed to clarify the prognostic significance of IMP3 expression in patients with NB. By microarray analysis, high IMP3 expression was found in patients with poor outcome. IMP3 expression in 90 NB samples was analyzed by immunohistochemical staining to correlate with clinical stages, histology, and patient outcome. Positive IMP3 expression was detected in 52 of 90 patients, and was significantly correlated with undifferentiated histology, advanced stages, MYCN amplification, and poor outcome. In subgroups, positive IMP3 expression could predict an even worse prognosis in patients with advanced disease, with normal MYCN status, or with MYCN amplification (P = 0.005, P = 0.001, and P = 0.033, respectively). The IMP3 expression decreased by induction of differentiation with retinoid acid treatment in SK-N-DZ and SK-N-SH cells in vitro. The invasion ability of NB cells also decreased as IMP3 knockdown by using RNA interference in vitro. In summary, high expression of IMP3 in NB might contribute to the undifferentiated phenotype and invasive behaviors, leading to a poor prognosis. Determining IMP3 expression in NB could help to improve a personalized therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / analysis
  • Cell Line, Tumor
  • Cell Proliferation
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • N-Myc Proto-Oncogene Protein
  • Neoplasm Invasiveness
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Neuroblastoma / genetics
  • Neuroblastoma / metabolism*
  • Neuroblastoma / mortality
  • Neuroblastoma / pathology*
  • Nuclear Proteins / biosynthesis
  • Oligonucleotide Array Sequence Analysis
  • Oncogene Proteins / biosynthesis
  • Prognosis
  • RNA Interference
  • RNA, Messenger / biosynthesis
  • RNA, Small Interfering
  • RNA-Binding Proteins / biosynthesis
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Tretinoin / pharmacology

Substances

  • Biomarkers, Tumor
  • IGF2BP3 protein, human
  • MYCN protein, human
  • N-Myc Proto-Oncogene Protein
  • Neoplasm Proteins
  • Nuclear Proteins
  • Oncogene Proteins
  • RNA, Messenger
  • RNA, Small Interfering
  • RNA-Binding Proteins
  • Tretinoin