Survivin mRNA levels are associated with biology of disease and patient survival in neuroblastoma: a report from the children's oncology group.
Alterations in apoptotic mechanisms favoring cell survival may be vital for modifying tumor behavior. Survivin, an inhibitor of apoptosis, and caspase 8, a proapoptotic enzyme, are key players in cellular apoptotic mechanisms. We investigated whether the levels of survivin and caspase 8 and the ratio between these 2 apoptotic factors correlate with tumor biology and predicts outcome in patients with neuroblastoma. Survivin and caspase 8 levels were quantified in 38 primary tumor specimens and analyzed individually and in relation to each other. High survivin expression and high survivin:caspase 8 ratios were associated with MYCN amplification, unfavorable histology, and high-risk group of disease (P<0.0008). High survivin mRNA levels were associated with worse overall survival (P=0.02) although the median follow up was only 22.6 months with a range of 1 day to 3.3 years. Low caspase 8 expression was associated with stage 4 disease, high-risk group, MYCN amplification, and unfavorable histology. Although the survivin:caspase 8 ratio was associated with these risk factors, the ratio did not improve the predictive value of survivin alone in this small series. Quantifying multiple apoptotic genes in neuroblastoma may supplement current risk stratification. Moreover, categorizing aberrant apoptotic gene expression in neuroblastoma may translate into novel therapeutic targets.
Miller
Michal A
MA
Department of Surgery, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
Ohashi
Kensuke
K
Zhu
Xiaoyan
X
McGrady
Patrick
P
London
Wendy B
WB
Hogarty
Michael
M
Sandler
Anthony D
AD
D053181:Caspase 8; D020169:Caspases / Q000096:biosynthesis / Q000235:genetics; D045744:Cell Line, Tumor; D005500:Follow-Up Studies; D005784:Gene Amplification; D020869:Gene Expression Profiling; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000235:genetics*; D000071447:N-Myc Proto-Oncogene Protein; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D009447:Neuroblastoma / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D015513:Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012307:Risk Factors; D015996:Survival Rate; D000077022:Survivin; D016896:Treatment Outcome
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; C459801:MYCN protein, human; D008869:Microtubule-Associated Proteins; D000071447:N-Myc Proto-Oncogene Protein; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D012333:RNA, Messenger; D000077022:Survivin; C505530:CASP8 protein, human; D053181:Caspase 8; D020169:Caspases