Transforming growth factor β-induced epithelial-to-mesenchymal signature predicts metastasis-free survival in non-small cell lung cancer

Edna Gordian, Eric A. Welsh, Nicholas Gimbrone, Erin M. Siegel, David Shibata, Ben C. Creelan, William Douglas Cress, Steven A. Eschrich, Eric B. Haura, Teresita Muñoz-Antonia

Research output: Contribution to journalArticle

Abstract

Transforming growth factor beta (TGFβ) plays a key role in regulating epithelial-to-mesenchymal transition (EMT). A gene expression signature (TGFβ-EMT) associated with TGFβ-induced EMT activities was developed using human Non-Small Cell Lung Carcinoma (NSCLC) cells treated with TGFβ-1 and subjected to Affymetrix microarray analysis. The final 105-probeset TGFβ-EMT signature covers 77 genes, and a NanoString assay utilized a subset of 60 of these genes (TGFβ-EMTN signature). We found that the TGFβ-EMT and TGFβ-EMT N gene signatures predicted overall survival (OS) and metastasis-free survival (MFS). The TGFβ-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 (ΔMFS TGFβ-EMT = -28.6%; ΔMFS TGFβ-EMT N = −25.2%) than at 5 years (ΔMFS TGFβ-EMT = -18.6%; ΔMFS TGFβ-EMT N = −11.8%). In addition, the TGFβ-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 TGFβ-EMT signature successfully discriminated lung cancer cell lines capable of undergoing EMT in response to TGFβ-1 and predicts MFS in lung adenocarcinomas. Thus, the TGFβ-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.

Original languageEnglish (US)
Pages (from-to)810-824
Number of pages15
JournalOncotarget
Volume10
Issue number8
StatePublished - Jan 1 2019

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Transforming Growth Factors
Epithelial-Mesenchymal Transition
Non-Small Cell Lung Carcinoma
Transforming Growth Factor beta
Neoplasm Metastasis
Survival
Lung Neoplasms
Genes
Neoplasms
Microarray Analysis
Transcriptome
Paraffin
Colonic Neoplasms
Formaldehyde

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Gordian, E., Welsh, E. A., Gimbrone, N., Siegel, E. M., Shibata, D., Creelan, B. C., ... Muñoz-Antonia, T. (2019). Transforming growth factor β-induced epithelial-to-mesenchymal signature predicts metastasis-free survival in non-small cell lung cancer. Oncotarget, 10(8), 810-824.

Transforming growth factor β-induced epithelial-to-mesenchymal signature predicts metastasis-free survival in non-small cell lung cancer. / Gordian, Edna; Welsh, Eric A.; Gimbrone, Nicholas; Siegel, Erin M.; Shibata, David; Creelan, Ben C.; Cress, William Douglas; Eschrich, Steven A.; Haura, Eric B.; Muñoz-Antonia, Teresita.

In: Oncotarget, Vol. 10, No. 8, 01.01.2019, p. 810-824.

Research output: Contribution to journalArticle

Gordian, E, Welsh, EA, Gimbrone, N, Siegel, EM, Shibata, D, Creelan, BC, Cress, WD, Eschrich, SA, Haura, EB & Muñoz-Antonia, T 2019, 'Transforming growth factor β-induced epithelial-to-mesenchymal signature predicts metastasis-free survival in non-small cell lung cancer', Oncotarget, vol. 10, no. 8, pp. 810-824.
Gordian, Edna ; Welsh, Eric A. ; Gimbrone, Nicholas ; Siegel, Erin M. ; Shibata, David ; Creelan, Ben C. ; Cress, William Douglas ; Eschrich, Steven A. ; Haura, Eric B. ; Muñoz-Antonia, Teresita. / Transforming growth factor β-induced epithelial-to-mesenchymal signature predicts metastasis-free survival in non-small cell lung cancer. In: Oncotarget. 2019 ; Vol. 10, No. 8. pp. 810-824.
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