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The Role of IMP3 Expression in Patients With Neuroblastoma

Sponsor
National Taiwan University Hospital (Other)
Overall Status
Completed
CT.gov ID
NCT01121419
Collaborator
(none)
1
Location
12
Duration (Months)

Study Details

Study Description

Brief Summary

Neuroblastoma (NB), a common cancer of early childhood originating from primitive sympathetic neural precursors, is characterized by the remarkable heterogeneity of clinical behaviors from spontaneous regression to rapid progression and death. The current therapeutic options are developed according to the Children's Oncology Group (COG) risk stratification criteria based on clinical and biological factors, including tumor stage, MYCN status, age at diagnosis, histology, and ploidy status. 1-2 The treatment strategies ranging from observation alone to intensive multimodality therapy depends on the risk stratification of three subgroups of low, intermediate, and high risk of death. Despite a number of molecular and biologic factors has been identified to predict the prognosis, MYCN amplification, which occurring in roughly 20% of primary NB, is one of the most powerful prognostic factors.3 The co-opting neurotrophin pathways including the neurotrophin receptors (TrkA, TrkB, and TrkC) and their ligands (NGF, BDNF, and neurotrophin-3, respectively), which regulate the differentiation, apoptosis, and growth of neural cells, are also important molecules related to the prognosis of NB.4 However, a proportion of patients with MYCN nonamplified NB still presents clinically aggressive progression similar to those of MYCN amplified tumors, suggesting that other unfavorable molecules exist for the inferior survival.5-6 The IGF-II RNA-binding protein 3 (IMP3), also known as L532S or K homology domain-containing protein overexpressed in cancer (KOC), is a member of RNA-binding protein family which includes IMP1, IMP2, and IMP3. The IMPs are primarily expressed during early embryogenesis and have been implicated in various post-transcriptional functions, including mRNA localization, cell growth, and cell migration during early embryogenesis.7-8 The IMP3 orthologue Vg1-RBP in Xenopus has also been described to promote migration of neural crest cells.9 Recently, the IMP3 is considered an oncofetal protein by increasing proliferation and invasion in various cancers including pancreas, kidney, and lung cancers.10-14 The expression of IMP3 is, however, low or undetectable in adjacent benign tissues.13 These lines of evidence indicate that IMP3 is capable of a potential biomarker to predict cancer progression and metastasis, and may serve as a target molecule for cancer therapy.14

oligonucleotide microarray is a powerful tool to do a genome-wide screening of candidate genes related to cancer prognosis.15 In this study, 22 primary NB tumors were subjected to oligonucleotide microarray analysis. Among the differentially expressed genes according to the patients' prognosis, IMP3 showed an especially high expression level in NB tumors carrying unfavorable prognosis. Further evaluation of IMP3 expression in a large sample size demonstrated that IMP3 expression could predict an unfavorable prognosis of NB patients independent of other biomarkers. Targeting of IMP3 expression in a NB cell line did suppress cell invasion ability, suggesting that IMP3 could not only be a prognostic factor, but also be a potential therapeutic target of NB.

Condition or Disease Intervention/Treatment Phase

    Study Design

    Study Type:
    Observational
    Observational Model:
    Cohort
    Time Perspective:
    Retrospective
    Official Title:
    The Role of IMP3 Expression in Patients With Neuroblastoma
    Study Start Date :
    Jan 1, 2008
    Actual Primary Completion Date :
    Jan 1, 2009
    Actual Study Completion Date :
    Jan 1, 2009

    Arms and Interventions

    Arm Intervention/Treatment
    Neuroblastoma

    Outcome Measures

    Primary Outcome Measures

      Eligibility Criteria

      Criteria

      Ages Eligible for Study:
      N/A to 18 Years
      Sexes Eligible for Study:
      All
      Accepts Healthy Volunteers:
      No
      Inclusion Criteria:
      • Neuroblastoma patients with complete follow-up and sufficient samples for study.
      Exclusion Criteria:

      • Neuroblastoma patients without complete follow-up

      • Neuroblastoma patients without sufficient samples for study.

      Contacts and Locations

      Locations

      Site City State Country Postal Code
      1 Wen-Ming Hsu Taipei Taiwan 100

      Sponsors and Collaborators

      • National Taiwan University Hospital

      Investigators

      • Principal Investigator: Wen-Ming Hsu, M.D, PhD, National Taiwan University Hospital

      Study Documents (Full-Text)

      None provided.

      More Information

      Publications

      None provided.
      Responsible Party:
      , ,
      ClinicalTrials.gov Identifier:
      NCT01121419
      Other Study ID Numbers:
      • 201002039R
      First Posted:
      May 12, 2010
      Last Update Posted:
      May 21, 2010
      Last Verified:
      May 1, 2010
      Keywords provided by , ,
      Neuroblastoma
      IMP3
      Prognosis
      Additional relevant MeSH terms:
      Neuroblastoma

      Study Results

      No Results Posted as of May 21, 2010