Identification and Validation of a Gene Expression Signature That Predicts Outcome in Adult Men With Germ Cell Tumors Export

@article{citeulike:6040308, abstract = {PurposeGerm 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 MethodsExpression 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. ResultsIn 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). ConclusionWe 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. 10.1200/JCO.2008.20.0386}, author = {Korkola, James E. and Houldsworth, Jane and Feldman, Darren R. and Olshen, Adam B. and Qin, Li-Xuan and Patil, Sujata and Reuter, Victor E. and Bosl, George J. and Chaganti, R. S. K.}, citeulike-article-id = {6040308}, citeulike-linkout-0 = {http://dx.doi.org/10.1200/JCO.2008.20.0386}, citeulike-linkout-1 = {http://jco.ascopubs.org/content/27/31/5240.abstract}, citeulike-linkout-2 = {http://jco.ascopubs.org/content/27/31/5240.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/19770384}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=19770384}, day = {1}, doi = {10.1200/JCO.2008.20.0386}, journal = {J Clin Oncol}, keywords = {biomarkers, gene\_expression\_signature, germ\_cell\_tumors, testis}, month = {November}, number = {31}, pages = {5240--5247}, posted-at = {2009-10-30 03:56:34}, priority = {2}, title = {Identification and Validation of a Gene Expression Signature That Predicts Outcome in Adult Men With Germ Cell Tumors}, url = {http://dx.doi.org/10.1200/JCO.2008.20.0386}, volume = {27}, year = {2009} }

TY - JOUR ID - citeulike:6040308 L3 - citeulike-article-id:6040308 N2 - PurposeGerm 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 MethodsExpression 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. ResultsIn 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). ConclusionWe 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. 10.1200/JCO.2008.20.0386 IS - 31 JF - J Clin Oncol EP - 5247 TI - Identification and Validation of a Gene Expression Signature That Predicts Outcome in Adult Men With Germ Cell Tumors VL - 27 SP - 5240 KW - biomarkers KW - gene_expression_signature KW - germ_cell_tumors KW - testis AU - Korkola, James AU - Houldsworth, Jane AU - Feldman, Darren AU - Olshen, Adam AU - Qin, Li-Xuan AU - Patil, Sujata AU - Reuter, Victor AU - Bosl, George AU - Chaganti, RSK PY - 2009/11/01/ UR - http://dx.doi.org/10.1200/JCO.2008.20.0386 ER -