Gene expression profiling for survival prediction in pediatric rhabdomyosarcomas: a report from the children's oncology group.
OBJECTIVE
We investigated whether tumors from diagnostic biopsies of primary rhabdomyosarcoma (RMS) contain relevant prognostic information in the form of gene expression signatures that can be used to model and predict outcome of patients.


METHODS
A 22,000-probe set microarray was used to evaluate 120 RMS specimens and correlate gene expression patterns to survival. Multivariate gene expression models or metagenes were developed using cross-validated Cox regression proportional hazards modeling and were evaluated using Kaplan-Meier analysis.


RESULTS
A 34-metagene, based on expression patterns of 34 genes, was highly predictive of outcome. It was not highly correlated with individual clinical risk factors such as patient age, stage, tumor size, or histology. However, it was correlated with a risk classification used by the Children's Oncology Group and the biologic subsets of alveolar histology tumors.


CONCLUSIONS
These data support further evaluation of RMS metagenes to discriminate patients with good prognosis from those with poor prognosis, with the potential to direct risk-adapted therapy.
Davicioni
Elai
E
Department of Pathology, Childrens Hospital Los Angeles, 4650 Sunset Blvd, Los Angeles, CA 90027, USA. triche@usc.edu
Anderson
James R
JR
Buckley
Jonathan D
JD
Meyer
William H
WH
Triche
Timothy J
TJ
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D020411:Oligonucleotide Array Sequence Analysis; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics; D011379:Prognosis; D016016:Proportional Hazards Models; D012208:Rhabdomyosarcoma / Q000235:genetics* / Q000401:mortality*
C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051761:Paired Box Transcription Factors