Abstract 1492: Systems analysis of epithelial-mesenchymal transition and cell invasion identifies functional gene signatures predictive of survival in lung cancer.

Abstract

Abstract We have implemented a systems approach to identify molecular features associated with mesenchymal or epithelial phenotypes and cell behavior in 38 lung adenocarcinoma cell lines that encompassed common known genomic alterations that drive the development of lung adenocarcinoma. Cell line characterization based on morphology, invasiveness, motility and cell-cell adhesion was integrated with proteomic, gene expression, microRNA and methylation profiles. Signatures were established from differential expression of transcripts and proteins in subsets of cell lines with mesenchymal and epithelial characteristics as well as high or low invasion and motility. The mesenchymal, invasion and migration signatures had common upregulation of genes or proteins related to cytoskeletal and actin-binding proteins. Sets of 148 and 74 transcripts corresponding to proteins that were overexpressed in mesenchymal cell lines and high invasive cell lines, respectively, were highly predictive of survival in three independent lung adenocarcinoma datasets. Subsets of 39 and 21 transcripts corresponding to cytoskeletal and acting binding proteins in the mesenchymal and invasive signatures were found to also predict survival in the three independent lung adenocarcinoma datasets, pointing to an association between cytoskeletal and actin binding proteins, a mesenchymal phenotype and tumor progression in lung adenocarcinoma. Citation Format: Mark J. Schliekelman, Ayumu Taguchi, Jun Zhu, Xudong Dai, Qing Zhang, Alice Chin, Chee-Hong Wong, Hong Wang, Adi Gazdar, Ite Laird-Offringa, Muneesh Tewari, Jean Paul Thiery, Samir Hanash. Systems analysis of epithelial-mesenchymal transition and cell invasion identifies functional gene signatures predictive of survival in lung cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1492. doi:10.1158/1538-7445.AM2013-1492