Stratification and delineation of gastric cancer signaling by in vitro transcription factor activity profiling and integrative genomics

Abstract Integrative functional genomic approaches are helpful in delineating the complex dysregulations in cancers. In the present study, in vitro activity profiling of 45 signaling pathway driven transcription factors in eight gastric cancer cell lines and direct comparison with genome-wide profiles of gastric tumors were performed and the integration resulted in the identification of three categories of factors/pathways: i) highly activated signaling pathways that stem from mutations are the critical oncogenic drivers, ii) constitutively activated stress responsive pathways which are activated not due to genetic alterations, and iii) consistently down-regulated nuclear receptor responsive factors. This functional profiling helps in discriminating therapeutic targets and signaling interactions.