Human Gene Set: LOPEZ_MESOTHELIOMA_SURVIVAL_WORST_VS_BEST_DN


Standard name LOPEZ_MESOTHELIOMA_SURVIVAL_WORST_VS_BEST_DN
Systematic name M7057
Brief description Genes higher expressed in the best 25 mesothelioma survivors compared to the 25 worst ones.
Full description or abstract Most gene expression profiling studies of mesothelioma have been based on relatively small sample numbers, limiting their statistical power. We did Affymetrix U133A microarray analysis on 99 pleural mesotheliomas, in which multivariate analysis showed advanced-stage, sarcomatous histology and P16/CDKN2A homozygous deletion to be significant independent adverse prognostic factors. Comparison of the expression profiles of epithelioid versus sarcomatous mesotheliomas identified many genes significantly overexpressed among the former, including previously unrecognized ones, such as uroplakins and kallikrein 11, both confirmed by immunohistochemistry. Examination of the gene expression correlates of survival showed that more aggressive mesotheliomas expressed higher levels of Aurora kinases A and B and functionally related genes involved in mitosis and cell cycle control. Independent confirmation of the negative effect of Aurora kinase B was obtained by immunohistochemistry in a separate patient cohort. A role for Aurora kinases in the aggressive behavior of mesotheliomas is of potential clinical interest because of the recent development of small-molecule inhibitors. We then used our data to develop microarray-based predictors of 1 year survival; these achieved a maximal accuracy of 68% in cross-validation. However, this was inferior to prognostic prediction based on standard clinicopathologic variables and P16/CDNK2A status (accuracy, 73%), and adding the microarray model to the latter did not improve overall accuracy. Finally, we evaluated three recently published microarray-based outcome prediction models, but their accuracies ranged from 63% to 67%, consistently lower than reported. Gene expression profiling of mesotheliomas is an important discovery tool, but its power in clinical prognostication has been overestimated.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 16540645   Authors: López-Ríos F,Chuai S,Flores R,Shimizu S,Ohno T,Wakahara K,Illei PB,Hussain S,Krug L,Zakowski MF,Rusch V,Olshen AB,Ladanyi M
Exact source Table 6AS: best25
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Source species Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
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identifier namespace		 AFFY_HG_U133
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