PURPOSE: We previously found that an epithelial-to-mesenchymal transition (EMT)-based gene expression signature was highly correlated with the first principal component ( @entity13704 ) of 326 @entity14 and was prognostic. This study was designed to improve these signatures for better prediction of @entity3 and outcome. EXPERIMENTAL DESIGN: A total of 468 @entity14 including all stages (I-IV) and metastatic lesions were used to develop a new prognostic score (  @entity13704 .EMT) by subtracting the EMT signature score from its correlated @entity13704 signature score. The score was validated on six other independent datasets with a total of 3,697 @entity5 . RESULTS:   @entity13704 .EMT was found to be far more predictive of @entity3 and outcome than its parent scores. It performed well in stages I to III, among microsatellite instability subtypes, and across multiple mutation-based subclasses, demonstrating a refined capacity to predict distant metastatic potential even in @entity5 with a "good" prognosis. For example, in the PETACC-3 clinical trial dataset, it predicted worse overall survival in an adjusted multivariable model for stage III @entity1 (HR standardized by interquartile range [IQR] = 1.50; 95% confidence interval, 1.25-1.81; P = 0.000016, N = 644). The improved performance of   @entity13704 .EMT was related to its propensity to identify epithelial-like subpopulations as well as mesenchymal-like subpopulations. Biologically, the signature was correlated positively with RAS signaling but negatively with mitochondrial metabolism.   @entity13704 .EMT was a "best of assessed" prognostic score when compared with 10 other known prognostic signatures. CONCLUSIONS: The study developed a prognostic signature score with a propensity to detect non-EMT features, including @entity5 stem cell-related properties, thereby improving its potential to predict @entity3 and poorer outcome in stage I-III @entity1 . Clin Cancer Res; 1-12.   2015 AACR.

A Composite Gene Expression Signature Optimizes Prediction of XXXX and Outcome.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity13704 :: ('5310', 'Gene') :: ['PC1'] @entity5 :: ('MESH:D009369', 'Disease') :: ['epithelial cancer', 'tumors'] @entity3 :: ('MESH:D009362', 'Disease') :: ['metastasis'] @entity14 :: ('MESH:D015179', 'Disease') :: ['colorectal cancer tumors']
@entity14 :: (MESH:D015179,Disease) :: ['Colorectal Cancer Metastasis']
