Prognostic significance of MDM2 gene expression in childhood neuroblastoma

Exp Oncol. 2015 Jun;37(2):111-5.

Abstract

Aim: To investigate the association of MDM2 expression at the mRNA levels in neuroblastoma with clinical features and unfavorable disease factors to determine the possibility of it usage as a prognostic marker of neuroblastoma.

Materials and methods: Total RNA and DNA were extracted from tumor tissue samples of total 91 neuroblastoma patients (mean age: 39.45 ± 4.81 months). MDM2 mRNA levels were detected with Q-PCR. TP53 gene deletion was detected with FISH method. MYCN amplification was detected with -Q-PCR analysis in fresh tumor samples and FISH in FFPE samples.

Results: We investigated the association of MDM2 mRNA expression with clinical outcome in neuroblastoma patients (n = 91). Kaplan - Meier curves showed a significant association of high MDM2 expression with poor event-free survival (p < 0.001). Clinical outcome of patients without MYCN amplification with low MDM2 expression was associated with better event-free survival than with high MDM2 expression (p < 0.001). Overexpression of MDM2 can be used as significant prognostic marker for patient stratification on risk groups and treatment optimization.

Conclusion: Our results showed that the high expression of MDM2 at mRNA levels is an important factor of neuroblastoma prognosis. It may be a valuable additional molecular marker in guiding specific therapy in MYCN non-amplified NB patients without TP53 gene deletion.

MeSH terms

  • Adolescent
  • Child
  • Disease-Free Survival
  • Gene Expression
  • Humans
  • Infant
  • Infant, Newborn
  • Kaplan-Meier Estimate
  • Neuroblastoma / genetics
  • Neuroblastoma / metabolism*
  • Neuroblastoma / mortality
  • Neuroblastoma / pathology
  • Peripheral Nervous System Neoplasms / genetics
  • Peripheral Nervous System Neoplasms / metabolism*
  • Peripheral Nervous System Neoplasms / mortality
  • Peripheral Nervous System Neoplasms / pathology
  • Prognosis
  • Proto-Oncogene Proteins c-mdm2 / genetics*
  • Proto-Oncogene Proteins c-mdm2 / metabolism
  • ROC Curve

Substances

  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2