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| Status |
Public on Oct 25, 2012 |
| Title |
An epithelial-mesenchymal transition (EMT) gene signature predicts resistance to erlotinib and PI3K pathway inhibitors and identifies Axl as a novel EMT marker in non-small cell lung cancer. |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Epithelial/mesenchymal transition (EMT) is associated with loss of cell adhesion molecules, such as E-cadherin, and increased invasion, migration, and proliferation in epithelial cancers. In non-small cell lung cancer (NSCLC), EMT is associated with greater resistance to EGFR inhibitors. However, its potential to predict response to other targeted drugs or chemotherapy has not been well characterized. The goal of this study was to develop a robust, platform-independent EMT gene expression signature and to investigate the association of EMT and drug response in NSCLC.
A 76-gene EMT signature was derived in 54 DNA-fingerprinted NSCLC cell lines and tested in an independent set of cell lines and in NSCLC patients from the BATTLE clinical trial. The signature classified cell lines as epithelial or mesenchymal independent of the microarray platform and correlated strongly with E-cadherin protein levels, as measured by reverse phase protein array. Higher protein expression of Rab25 (in epithelial lines) and Axl (in mesenchymal lines), two signature genes associated with in EMT in other cancer types, was also confirmed. Mesenchymal cell lines demonstrated significantly greater resistance to EGFR inhibition, independent of EGFR mutation status and were more resistant to drugs targeting the PI3K/Akt pathway. We observed no association between EMT and response to cytotoxic chemotherapies, including cisplatin, pemetrexed, and docetaxel monotherapy and/or doublets (p-values ≥0.2). In NSCLC patients, the EMT signature predicted 8-week disease control in the erlotinib arm, but not in other treatment arms. In conclusion, we have developed a robust EMT signature that predicts resistance to EGFR inhibitors and PI3K/Akt pathway inhibitors.
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| Overall design |
Gene expression profiles were measured in 131 core biopsies from patients with refractory non-small cell lung cancer in the Biomarker-integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) trial. We used the BATTLE dataset to test an EMT gene expression signature trained in cell lines and independant of the microarray platform.
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| Contributor(s) |
Saintigny P, Wistuba II, Heymach JV, Kim ES, Lippman SM, Herbst RS, Hong WK, Lee JJ, Coombes KR, Mao L |
| Citation(s) |
23091115 |
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| Submission date |
Oct 19, 2011 |
| Last update date |
Jul 26, 2018 |
| Contact name |
Pierre Saintigny |
| E-mail(s) |
psaintig@mdanderson.org
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| Organization name |
The University of Texas M.D. Anderson Cancer Center
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| Department |
Thoracic / Head and Neck Medical Oncology
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| Street address |
1515 Holcombe
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| City |
Houston |
| ZIP/Postal code |
77030 |
| Country |
USA |
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| Platforms (1) |
| GPL6244 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (131)
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| Relations |
| BioProject |
PRJNA149495 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE33072_RAW.tar |
594.9 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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