Identification and validation of a gene expression signature that predicts outcome in adult men with germ cell tumors Journal Article

Authors: Korkola, J. E.; Houldsworth, J.; Feldman, D. R.; Olshen, A. B.; Qin, L. X.; Patil, S.; Reuter, V. E.; Bosl, G. J.; Chaganti, R. S. K.
Article Title: Identification and validation of a gene expression signature that predicts outcome in adult men with germ cell tumors
Abstract: Purpose Germ cell tumor (GCT) is the most common malignancy in young adult men. Currently, patients are risk-stratified on the basis of clinical presentation and serum tumor markers. The introduction of molecular markers could improve outcome prediction. Patients and Methods Expression profiling was performed on 74 nonseminomatous GCTs (NSGCTs) from cisplatin-treated patients (ie, training set) and on 34 similarly treated patients with NSGCTs (ie, validation set). A gene classifier was developed by using prediction analysis for microarrays (PAM) for the binary end point of 5-year overall survival (OS). A predictive score was developed for OS by using the univariate Cox model. Results In the training set, PAM identified 140 genes that predicted 5-year OS (cross-validated classification rate, 60%). The PAM model correctly classified 90% of patients in the validation set. Patients predicted to have good outcome had significantly longer survival than those with poor predicted outcome (P < .001). For the OS end point, a 10-gene model had a predictive accuracy (ie, concordance index) of 0.66 in the training set and a concordance index of 0.83 in the validation set. Dichotomization of the samples on the basis of the median score resulted in significant differences in survival (P = .002). For both end points, the gene-based predictor was an independent prognostic factor in a multivariate model that included clinical risk stratification (P < .01 for both). Conclusion We have identified gene expression signatures that accurately predict outcome in patients with GCTs. These predictive genes should be useful for the prediction of patient outcome and could provide novel targets for therapeutic intervention.
Keywords: survival; cisplatin; chemotherapy; classification; etoposide; randomized-trial; embryonal carcinoma-cells; in-vivo differentiation; myopodin
Journal Title: Journal of Clinical Oncology
Volume: 27
Issue: 31
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2009-11-01
Start Page: 5240
End Page: 5247
Language: English
ACCESSION: ISI:000271274300022
DOI: 10.1200/jco.2008.20.0386
PMCID: PMC3651602
PUBMED: 19770384
Notes: --- - Article - "Source: Wos"
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MSK Authors
  1. Sujata Patil
    383 Patil
  2. James E Korkola
    24 Korkola
  3. Darren Richard Feldman
    171 Feldman
  4. Li-Xuan Qin
    114 Qin
  5. Adam B Olshen
    107 Olshen
  6. Victor Reuter
    900 Reuter
  7. Raju S K Chaganti
    262 Chaganti
  8. George Bosl
    255 Bosl