HsMAD2 mRNA expression may be a predictor of sensitivity to paclitaxel and survival in neuroblastoma

Pediatr Surg Int. 2011 Feb;27(2):217-23. doi: 10.1007/s00383-010-2780-5.

Abstract

Purpose: We investigated the associations between hsMAD2 mRNA expression in tumor cells and sensitivity to paclitaxel or patient prognosis in neuroblastoma.

Methods: Fifty-one formalin-fixed paraffin-embedded tumor samples were manually microdissected to collect tumor cells, and RNA was purified. Nineteen clinical samples of advanced neuroblastoma showed appropriate quality of the isolated RNA for real-time reverse transcription-polymerase chain reaction (RT-PCR) analyses. The hsMAD2 expression levels were determined by real-time RT-PCR in 4 neuroblastoma cell lines and 19 clinical samples. The sensitivity to paclitaxel was assessed by WST-8 colorimetric assays and flow cytometry. HsMAD2 expression of the clinical samples was investigated for its association with prognosis in advanced neuroblastoma patients.

Results: There was a significant positive correlation between hsMAD2 mRNA expression and the sensitivity to paclitaxel in four neuroblastoma cell lines. High hsMAD2 expression may be correlated with paclitaxel-induced apoptosis. Kaplan-Meier survival curves were stratified by hsMAD2 expression using the median value as a cut-off point and analyzed for prognostic significance by the log-rank test (P = 0.0467). Furthermore, multivariate survival analysis revealed that only hsMAD2 expression had a significant impact on the overall survival rate.

Conclusions: Our results may warrant clinical application of paclitaxel in neuroblastoma treatment for poor prognosis patients.

Publication types

  • Comparative Study

MeSH terms

  • Abdominal Neoplasms / drug therapy
  • Abdominal Neoplasms / genetics
  • Abdominal Neoplasms / mortality
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Apoptosis
  • Calcium-Binding Proteins / biosynthesis
  • Calcium-Binding Proteins / genetics*
  • Cell Cycle Proteins / biosynthesis
  • Cell Cycle Proteins / genetics*
  • Cell Line, Tumor
  • Child, Preschool
  • Female
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Infant
  • Infant, Newborn
  • Japan / epidemiology
  • Mad2 Proteins
  • Male
  • Neuroblastoma / drug therapy
  • Neuroblastoma / genetics*
  • Neuroblastoma / mortality
  • Paclitaxel / therapeutic use*
  • Prognosis
  • RNA, Messenger / genetics*
  • Repressor Proteins / biosynthesis
  • Repressor Proteins / genetics*
  • Retrospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Rate / trends
  • Thoracic Neoplasms / drug therapy
  • Thoracic Neoplasms / genetics
  • Thoracic Neoplasms / mortality

Substances

  • Antineoplastic Agents, Phytogenic
  • Calcium-Binding Proteins
  • Cell Cycle Proteins
  • MAD2L1 protein, human
  • Mad2 Proteins
  • RNA, Messenger
  • Repressor Proteins
  • Paclitaxel