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Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids
Published on: November 22, 2021
Epithelial phenotype as a predictive marker for response to EGFR-TKIs in non-small cell lung cancer patients with
Shengxiang Ren1, Chunxia Su, Zhaoye Wang
1Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Tongji University Medical School Cancer Institute, Shanghai, People's Republic of China.
Abstract:
Epithelial-to-mesenchymal transition (EMT) has profound impacts on cancer progression and also on drug resistance, including epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Nowadays, there is still no predictive biomarker identified for the use of EGFR-TKIs in non-small cell lung cancer (NSCLC) patients with wild-type EGFR. To clarify the role of EMT phenotype as a predictive marker for EGFR-TKI, we performed a retrospective study in 202 stage IV or recurrent NSCLC patients receiving gefitinib or erlotinib therapy from June 2008 to September 2012 in our institute. Clinical data and EGFR mutational status were collected, while epithelial, epithelial to mesenchymal, not specified or mesenchymal phenotype were classified according to EMT markers such as E-cadherin, fibronectin, N-cadherin and vimentin by immunohistochemistry. Epithelial phenotype was more frequently found in patients with EGFR mutation (p = 0.044). Epithelial phenotype was associated with a significantly higher objective response rate (23.5 vs. 11.1 vs. 0.0 vs. 2.4%, p = 0.011), longer progression-free survival (4.4 vs. 1.9 vs. 1.7 vs. 1.0 months, p < 0.001) and longer overall survival (11.5 vs. 8.9 vs. 4.5 vs. 4.9 months, p < 0.001) compared to epithelial to mesenchymal, not specified and mesenchymal phenotype in the wild-type EGFR subgroup. In the subgroup with EGFR mutation, the trend remained but without a statistically significant difference. In conclusion, epithelial phenotype was more likely expressed in patients with EGFR mutation and was associated with a better outcome in advanced NSCLC patients with wild-type EGFR, which indicates that the EMT phenotype might be a potential marker to guide EGFR-TKI therapy in this population.
Insights
The epithelial phenotype, indicative of epithelial-to-mesenchymal transition (EMT), may predict response to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC) patients without EGFR mutations.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Epithelial-to-mesenchymal transition (EMT) influences cancer progression and drug resistance, including to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs).
- A predictive biomarker for EGFR-TKI efficacy in non-small cell lung cancer (NSCLC) patients with wild-type EGFR remains elusive.
- Understanding the role of EMT phenotypes in predicting treatment response is crucial for personalized NSCLC therapy.
Purpose of the Study:
- To investigate the epithelial-to-mesenchymal transition (EMT) phenotype as a predictive biomarker for EGFR-TKI therapy in advanced NSCLC patients.
- To correlate EMT markers with clinical outcomes in NSCLC patients treated with gefitinib or erlotinib.
- To determine if EMT status can guide EGFR-TKI selection in wild-type EGFR NSCLC.
Main Methods:
- Retrospective study of 202 stage IV or recurrent NSCLC patients treated with gefitinib or erlotinib.
- Classification of EMT phenotypes (epithelial, epithelial to mesenchymal, not specified, mesenchymal) using immunohistochemistry for E-cadherin, fibronectin, N-cadherin, and vimentin.
- Analysis of clinical data, EGFR mutational status, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).
Main Results:
- Epithelial phenotype was more frequent in patients with EGFR mutations (p = 0.044).
- In wild-type EGFR NSCLC, the epithelial phenotype showed significantly higher ORR (23.5% vs. 11.1% vs. 0.0% vs. 2.4%, p = 0.011), longer PFS (4.4 vs. 1.9 vs. 1.7 vs. 1.0 months, p < 0.001), and longer OS (11.5 vs. 8.9 vs. 4.5 vs. 4.9 months, p < 0.001) compared to other EMT phenotypes.
- A similar trend was observed in the EGFR-mutated subgroup, though not statistically significant.
Conclusions:
- The epithelial phenotype is associated with EGFR mutations and predicts a better response to EGFR-TKIs in advanced NSCLC patients with wild-type EGFR.
- EMT phenotype may serve as a potential predictive biomarker to guide EGFR-TKI therapy selection in specific NSCLC patient populations.
- Further research is warranted to validate EMT status as a clinical biomarker for EGFR-TKI treatment in NSCLC.
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