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Gene Expression Profiles Predict Survival and Progression of Pleural Mesothelioma
Purpose: Clinical outcomes for malignant pleural mesothelioma (MPM) patients having surgery are imprecisely predicted by histopathology and intraoperative staging. We hypothesized that gene expression profiles could predict time to progression and survival in surgically cytoreduced pleural mesotheli...
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Published in: | Clinical cancer research 2004-02, Vol.10 (3), p.849-859 |
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Main Authors: | , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Purpose: Clinical outcomes for malignant pleural mesothelioma (MPM) patients having surgery are imprecisely predicted by histopathology
and intraoperative staging. We hypothesized that gene expression profiles could predict time to progression and survival in
surgically cytoreduced pleural mesothelioma of all stages.
Experimental Design: Gene expression analyses from 21 MPM patients having cytoreductions and identical postoperative adjuvant therapy were performed
using the U95 Affymetrix gene chip. Using both dChip and SAM, neural networks constructed a common 27 gene classifier, which
was associated with either the high-risk and low-risk group of patients. Data were validated using real-time PCR and immunohistochemical
staining. The 27 gene classifier was also used for validation in a separate set of 17 MPM patients from another institution.
Results: The groups predicted by the gene classifier recapitulated the actual time to progression and survival of the test set with
95.2% accuracy using 10-fold cross-validation. Clinical outcomes were independent of histology, and heterogeneity of progression
and survival in early stage patients was defined by the classifier. The gene classifier had a 76% accuracy in the separate
validation set of MPMs.
Conclusions: These data suggest that pretherapy gene expression analysis of mesothelioma biopsies may predict which patients may benefit
from a surgical approach. |
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ISSN: | 1078-0432 1557-3265 |
DOI: | 10.1158/1078-0432.CCR-0607-3 |