HsMAD2 mRNA expression may be a predictor of sensitivity to paclitaxel and survival in neuroblastoma.
OBJECTIVE
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.
Department 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
Kohei
K
Otake
Keiichi
K
Uchida
Kouji
K
Tanaka
Yuhki
Y
Koike
Mikihiro
M
Inoue
Kohei
K
Matsushita
Motoko
M
Ueeda
Kiyoshi
K
Hashimoto
Takahito
T
Kitajima
Yoshihiro
Y
Komada
Masato
M
Kusunoki
D000008:Abdominal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D017209:Apoptosis; D002135:Calcium-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics*; D045744:Cell Line, Tumor; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007564:Japan / Q000453:epidemiology; D064246:Mad2 Proteins; D008297:Male; D009447:Neuroblastoma / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D017239:Paclitaxel / Q000627:therapeutic use*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics*; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics*; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate / Q000639:trends; D013899:Thoracic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000401:mortality
D000972:Antineoplastic Agents, Phytogenic; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; C577697:MAD2L1 protein, human; D064246:Mad2 Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D017239:Paclitaxel