Comprehensive molecular characterization of the hippo signaling pathway in cancer

Hippo signaling has been recognized as a key tumor suppressor pathway. Here, we perform a comprehensive molecular characterization of 19 Hippo core genes in 9,125 tumor samples across 33 cancer types using multidimensional “omic” data from The Cancer Genome Atlas. We identify somatic drivers among Hippo genes and the related microRNA (miRNA) regulators, and using functional genomic approaches, we experimentally characterize YAP and TAZ mutation effects and miR-590 and miR-200a regulation for TAZ. Hippo pathway activity is best characterized by a YAP/TAZ transcriptional target signature of 22 genes, which shows robust prognostic power across cancer types. Our elastic-net integrated modeling further reveals cancer-type-specific pathway regulators and associated cancer drivers. Our results highlight the importance of Hippo signaling in squamous cell cancers, characterized by frequent amplification of YAP/TAZ, high expression heterogeneity, and significant prognostic patterns. This study represents a systems-biology approach to characterizing key cancer signaling pathways in the post-genomic era

Risk prediction scores for postoperative mortality after esophagectomy: validation of different models

© 2008 The Society for Surgery of the Alimentary TractBackground Different prediction models for operative mortality after esophagectomy have been developed. The aim of this study is to independently validate prediction models from Philadelphia, Rotterdam, Munich, and the ASA. Methods The scores were validated using logistic regression models in two cohorts of patients undergoing esophagectomy for cancer from Switzerland (n = 170) and Australia (n = 176). Results All scores except ASA were significantly higher in the Australian cohort. There was no significant difference in 30-day mortality or in-hospital death between groups. The Philadelphia and Rotterdam scores had a significant predictive value for 30-day mortality (p = 0.001) and in-hospital death (p = 0.003) in the pooled cohort, but only the Philadelphia score had a significant prediction value for 30-day mortality in both cohorts. Neither score showed any predictive value for in-hospital death in Australians but were highly significant in the Swiss cohort. ASA showed only a significant predictive value for 30-day mortality in the Swiss. For in-hospital death, ASA was a significant predictor in the pooled and Swiss cohorts. The Munich score did not have any significant predictive value whatsoever. Conclusion None of the scores can be applied generally. A better overall predictive score or specific prediction scores for each country should be developed.U. Zingg, C. Langton, B. Addison, B. P. L. Wijnhoven, J. Forberger, S. K. Thompson, A. J. Esterman and D. I. Watso