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HsMAD2 mRNA expression may be a predictor of sensitivity to paclitaxel and survival in neuroblastoma
Kohei Otake1, Keiichi Uchida, Kouji Tanaka
1Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, Edobashi 2-174, Tsu, Mie, 514-8507, Japan. kohei815@clin.medic.mie-u.ac.jp
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.
