%0 Journal Article
%T Transforming growth factor ¦Â-induced epithelial-to-mesenchymal signature predicts metastasis-free survival in non-small cell lung cancer
%A Ben C. Creelan
%A David Shibata
%A Edna Gordian
%A Eric A. Welsh
%A Eric B. Haura
%A Erin M. Siegel
%A Nicholas Gimbrone
%A Steven A. Eschrich
%A Teresita Mu£¿oz-Antonia
%A William Douglas Cress
%J Archive of "Oncotarget".
%D 2019
%R 10.18632/oncotarget.26574
%X Transforming growth factor beta (TGF¦Â) plays a key role in regulating epithelial-to-mesenchymal transition (EMT). A gene expression signature (TGF¦Â-EMT) associated with TGF¦Â-induced EMT activities was developed using human Non-Small Cell Lung Carcinoma (NSCLC) cells treated with TGF¦Â-1 and subjected to Affymetrix microarray analysis. The final 105-probeset TGF¦Â-EMT signature covers 77 genes, and a NanoString assay utilized a subset of 60 of these genes (TGF¦Â-EMTN signature). We found that the TGF¦Â-EMT and TGF¦Â-EMTN gene signatures predicted overall survival (OS) and metastasis-free survival (MFS). The TGF¦Â-EMT signature was validated as prognostic of 5-year MFS in 3 cohorts: a 133 NSCLC tumor dataset (P = 0.0002), a NanoString assays of RNA isolated from formalin-fixed paraffin-embedded samples from these same tumors (P = 0.0015), and a previously published NSCLC MFS dataset (P = 0.0015). The separation between high and low metastasis signature scores was higher at 3 years (¦¤MFS TGF¦Â-EMT = £¿28.6%; ¦¤MFS TGF¦Â-EMTN = £¿25.2%) than at 5 years (¦¤MFS TGF¦Â-EMT = £¿18.6%; ¦¤MFS TGF¦Â-EMTN = £¿11.8%). In addition, the TGF¦Â-EMT signature correlated with whether the cancer had already metastasized or not at time of surgery in a colon cancer cohort. The results show that the TGF¦Â-EMT signature successfully discriminated lung cancer cell lines capable of undergoing EMT in response to TGF¦Â-1 and predicts MFS in lung adenocarcinomas. Thus, the TGF¦Â-EMT signature has the potential to be developed as a clinically relevant predictive biomarker, for example to identify those patients with resected early stage lung cancer who may benefit from adjuvant therapy
%K non-small cell lung cancer
%K epithelial-to-mesenchymal transition
%K EMT
%K metastasis
%K colon cancer
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6368226/