@entity30351 Is Highly Expressed in Cancer-Associated Fibroblasts and Associates to Poor XXXX Survival.

@entity1 @entity13808 @entity82 @entity5 @entity30351 @entity694
PURPOSE: Cancer-associated fibroblasts (CAF) are major mediators in @entity5 microenvironment. We investigated the changes in protein expression in @entity694 -associated fibroblasts compared with normal fibroblasts (NF) in the context of searching for prognostic biomarkers, particularly for stage II @entity1 . EXPERIMENTAL DESIGN: @entity13808 and NFs isolated from @entity694 @entity1 were used to identify differentially expressed proteins using quantitative proteomics. Stromal expression of deregulated proteins was analyzed by IHC. Prognostic impact was studied using external gene-expression datasets for training, then quantitative PCR and IHC for validation in different cohorts of @entity1 . Combined datasets were used for prediction of risk assessment at stages II and III. RESULTS: A desmoplastic signature composed of 32 proteins, highly specific for stromal components in @entity694 , was identified. These proteins were enriched for extracellular matrix organization components, TGFb signaling pathway, @entity82 , and wound-healing proteins. The expression in @entity13808 of 11 upregulated proteins and four downregulated proteins, selected for biomarker validation, was verified by orthogonal techniques. @entity30351 displayed a high prognostic impact by using external independent datasets and further validation in two different cohorts of @entity1 . High expression of @entity30351 was associated with higher recurrence P = 0.001 HR, 5.38 [95% confidence interval (CI), 1.70-17.01] and overall survival P = 0.001 HR, 8.52 (95% CI, 1.90-38.29). IHC analysis revealed a prognostic value for @entity30351 in stage II @entity1 . CONCLUSIONS: We identified @entity30351 to be associated with the outcome of @entity694 @entity1 . Furthermore, it can be used to stratify @entity1 at stages II and III for further therapeutic decisions. Clin Cancer Res; 1-11.   2015 AACR.
