|
|
Gene expression profiling
of neuroblastoma: Analysis of nonmetastatic versus metastatic tumors
J. Mora, M. Alaminos, N.-K. Cheung, J. Rios, W. Gerald
Hospital Sant Joan de Deu de Barcelona, Barcelona, Spain; Centro Nacional de
Investigaciones oncologicas, Madrid, Spain; Memorial Sloan-Kettering Cancer
Center, New York, NY; Laboratori de Bioestadística i Epidemiologia, Barcelona,
Spain
Background. Previously we reported a significant distinction
in gene expression profile between neuroblastoma (NB) tumors and cell lines, and
stroma-rich and stroma-poor NB tumors.
Tumors clustered into 2 groups correlating with clinically defined prognostic
groups of favorable and unfavorable tumors.
In this study we analyzed tumors with and without clinically proved metastatic
potential.
Methods. We present the
analysis of 25 locoregional and 27 stage 4 tumors all stroma poor and >1 year
of age.
Microarray analysis was carried out using Affymetrix Genechip Human Genome U95
SetTM with features for 63,175 gene/EST.
To calculate the ability of individual genes to distinguish between sample
groups we used
1. Calculation of maximal variability and >3 standard deviation between
groups and
2. Step-down permutation and false discovery rate methods.
For multivariate analysis, unsupervised methods like SOMS, PCA, K-nearest
neighboring, and hierarchical clustering were applied.
Results. By contrast
analysis, 61out of 12,000 known annotated genes from chip A were differentially
expressed in LR cases compared to stage 4.
By permutation analysis only 3 out of the 12000 annotated genes showed
statistical significance.
Multivariate analysis showed a poor distinction between LR and stage 4 tumors
with a third of samples classifying in the wrong groups.
Classification models build to distinguish groups using support vector machines,
k-nearest neighboring and log regression showed a cross validation accuracy that
ranged from 76 to 89%.
Conclusions. The gene
expression profiles of tumors presenting as LR or disseminated disease suggest
the existence of more than 2 groups of tumors.
A "metastatic" gene expression profile could not be detected.
Copyright 2004 American Society of Clinical Oncology All rights reserved
worldwide.
Source: http://www.asco.org/ac/1,1003,_12-002636-00_18-0026-00_19-002046,00.asp
|
