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Updated: Apr 19, 2026
Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids
Published on: November 22, 2021
Microarray expression profile of long non-coding RNAs in EGFR-TKIs resistance of human non-small cell lung cancer
Ningning Cheng1, Xuefei Li2, Chao Zhao2
1Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University, Tongji University Medical School Cancer Institute, Shanghai 200433, P.R. China.
Abstract:
The application of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is limited by drug resistance in non-small cell lung cancer (NSCLC). Long non-coding RNAs (lncRNAs) are known to be involved in tumor development and metastasis, as well as chemotherapy resistance. To gain insight into the molecular mechanisms of EGFR-TKIs resistance, EGFR-TKIs‑sensitive and ‑resistant human lung cancer cells were analyzed by lncRNA microarray. In the present study, we found a total of 22,587 lncRNAs expressed in lung cancer cells. Of these, the expression level of 1,731 lncRNAs was upregulated >2-fold compared with gefitinib-sensitive cells while that of 2,936 was downregulated. Bioinformatics analysis (GO and pathway analyses) revealed that some classical pathways participating in cell proliferation and apoptosis were aberrantly expressed in these cells (P-value cut-off was 0.05). Enhancer-like lncRNAs and their nearby coding genes were analyzed. Six lncRNAs were identified as potential enhancers. Several lncRNAs were validated in lung cancer cell lines using RT-qPCR. To the best of our knowledge, the results showed for the first time that differentially expressed lncRNAs responded to EGFR-TKIs resistance in NSCLC cells. LncRNAs may therefore be novel candidate biomarkers and potential targets for EGFR-TKIs therapy in the future.
Insights
Drug resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) was investigated. Differentially expressed long non-coding RNAs (lncRNAs) were identified, suggesting their role in TKI resistance.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) efficacy in non-small cell lung cancer (NSCLC) is hindered by drug resistance.
- Long non-coding RNAs (lncRNAs) are implicated in cancer progression and chemotherapy resistance.
Purpose of the Study:
- To explore the molecular mechanisms underlying EGFR-TKI resistance in NSCLC.
- To identify novel long non-coding RNAs (lncRNAs) associated with EGFR-TKI resistance.
Main Methods:
- lncRNA microarray analysis of EGFR-TKI-sensitive and -resistant human lung cancer cells.
- Bioinformatics analyses including Gene Ontology (GO) and pathway analysis.
- Validation of selected lncRNAs using RT-qPCR.
Main Results:
- A total of 22,587 lncRNAs were identified in lung cancer cells.
- 1,731 lncRNAs were upregulated and 2,936 were downregulated in resistant cells compared to sensitive cells.
- Aberrant expression of pathways involved in cell proliferation and apoptosis was observed.
- Six lncRNAs were identified as potential enhancers.
Conclusions:
- This study reveals differentially expressed lncRNAs in response to EGFR-TKI resistance in NSCLC cells for the first time.
- lncRNAs represent potential novel biomarkers for predicting TKI resistance.
- lncRNAs may serve as future therapeutic targets for overcoming EGFR-TKI resistance in NSCLC.
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