%0 Journal Article
%T Colon cancer molecular subtypes identified by expression profiling and associated to stroma, mucinous type and different clinical behavior
%A Beatriz Perez-Villamil
%A Alejandro Romera-Lopez
%A Susana Hernandez-Prieto
%A Guillermo Lopez-Campos
%A Antonio Calles
%A Jose-Antonio Lopez-Asenjo
%A Julian Sanz-Ortega
%A Cristina Fernandez-Perez
%A Javier Sastre
%A Rosario Alfonso
%A Trinidad Caldes
%A Fernando Martin-Sanchez
%A Eduardo Diaz-Rubio
%J BMC Cancer
%D 2012
%I BioMed Central
%R 10.1186/1471-2407-12-260
%X Hierarchical clustering was performed for class discovery in 88 colon tumors (stages I to IV). Pathways analysis and correlations between clinical parameters and our classification were analyzed. Tumor subtypes were validated using an external set of 78 patients. A 167 gene signature associated to the main subtype was generated using the 3-Nearest-Neighbor method. Coincidences with other prognostic predictors were assesed.Hierarchical clustering identified four robust tumor subtypes with biologically and clinically distinct behavior. Stromal components (p£¿<£¿0.001), nuclear ¦Â-catenin (p£¿=£¿0.021), mucinous histology (p£¿=£¿0.001), microsatellite-instability (p£¿=£¿0.039) and BRAF mutations (p£¿<£¿0.001) were associated to this classification but it was independent of Dukes stages (p£¿=£¿0.646). Molecular subtypes were established from stage I. High-stroma-subtype showed increased levels of genes and altered pathways distinctive of tumour-associated-stroma and components of the extracellular matrix in contrast to Low-stroma-subtype. Mucinous-subtype was reflected by the increased expression of trefoil factors and mucins as well as by a higher proportion of MSI and BRAF mutations. Tumor subtypes were validated using an external set of 78 patients. A 167 gene signature associated to the Low-stroma-subtype distinguished low risk patients from high risk patients in the external cohort (Dukes B and C:HR£¿=£¿8.56(2.53-29.01); Dukes B,C and D:HR£¿=£¿1.87(1.07-3.25)). Eight different reported survival gene signatures segregated our tumors into two groups the Low-stroma-subtype and the other tumor subtypes.We have identified novel molecular subtypes in colon cancer with distinct biological and clinical behavior that are established from the initiation of the tumor. Tumor microenvironment is important for the classification and for the malignant power of the tumor. Differential gene sets and biological pathways characterize each tumor subtype reflecting underlying mechanisms of carcinogenes
%K Colon cancer
%K Microarray gene expression
%K Molecular classification
%K Stroma
%K Survival
%U http://www.biomedcentral.com/1471-2407/12/260/abstract