Related Experiment Video
Updated: Feb 18, 2026
Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
Published on: August 11, 2017
Plasma microRNA alterations between EGFR-activating mutational NSCLC patients with and without primary resistance to
Yihan Ma1, Xiaoyan Pan1,2, Peiqi Xu3
1Xiamen Cancer Hospital the First Affiliated Hospital of Xiamen University, 361003 Fujian, China.
Abstract:
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have obtained excellent therapeutic effects against non-small cell lung cancer (NSCLC) harboring activating EGFR mutations. However, some patients have exhibited primary resistance which becomes a major obstacle in effective treatment of NSCLC. The mechanisms of EGFR-TKIs resistance involved are still poorly understood. Many studies suggest that miRNAs play an important role in regulating drug sensitivity of EGFR-TKIs. The aim of the present study was to examine differentially expressed miRNAs in plasma between EGFR-TKIs sensitive and EGFR-TKIs primary resistance patients. MiRNA microarray of plasma from patients' blood identified 16 differentially expressed miRNAs of which 15 (hsv2-miR-H19, hsa-miR-744-5p, hsa-miR-3196, hsa-miR-3153, hsa-miR-4791, hsa-miR-4803, hsa-miR-4796-3p, hsa-miR-372-5p, hsa-miR-138-2-3p, hsa-miR-16-1-3p, hsa-miR-1469, hsa-miR-585-3p, ebv-miR-BART14-5p, hsa-miR-769-3p, hsa-miR-548aq-5p) were down regulated while only hsa-miR-503-3p was up regulated in primary resistant patients' plasma. Volcano plot and hierarchical clustering were performed to examine the accuracy of the miRNAs. Then validation with quantitative real-time PCR was performed and the result was in accordance with the array data. Functional analysis of these differentially expressed miRNAs with Ingenuity Pathway Analysis (IPA) revealed a common signaling network including MYC, CCND1, IGF1 and RELA. In conclusion, our finding may play important role in understanding the mechanisms underlying the problem and should be further evaluated as potential biomarkers in primary resistance of NSCLC.
Insights
MicroRNAs in plasma may predict primary resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC). Identifying these differentially expressed miRNAs could improve treatment strategies for NSCLC patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are effective for non-small cell lung cancer (NSCLC) with activating EGFR mutations.
- Primary resistance to EGFR-TKIs presents a significant challenge in NSCLC treatment, with underlying mechanisms not fully understood.
- MicroRNAs (miRNAs) are implicated in regulating cellular responses and drug sensitivity.
Purpose of the Study:
- To investigate differentially expressed miRNAs in plasma as potential indicators of primary resistance to EGFR-TKIs in NSCLC patients.
- To identify specific miRNAs associated with EGFR-TKI resistance for improved therapeutic strategies.
Main Methods:
- Plasma miRNA expression profiling using miRNA microarrays in EGFR-TKI sensitive versus primary resistant NSCLC patients.
- Validation of differentially expressed miRNAs using quantitative real-time PCR (qRT-PCR).
- Functional analysis of identified miRNAs using Ingenuity Pathway Analysis (IPA) to explore associated signaling networks.
Main Results:
- Sixteen differentially expressed miRNAs were identified: 15 downregulated and 1 upregulated in plasma from primary resistant NSCLC patients compared to sensitive ones.
- Validation confirmed the array data, indicating significant differences in miRNA expression profiles.
- Functional analysis revealed a common signaling network involving MYC, CCND1, IGF1, and RELA, potentially linked to EGFR-TKI resistance.
Conclusions:
- Plasma miRNA expression profiles differ between EGFR-TKI sensitive and primary resistant NSCLC patients.
- These differentially expressed miRNAs may play a crucial role in the mechanisms of primary EGFR-TKI resistance in NSCLC.
- The identified miRNAs hold potential as predictive biomarkers for primary resistance to EGFR-TKIs in NSCLC.
More Related Videos
08:49Exosomal miRNA Analysis in Non-small Cell Lung Cancer NSCLC Patients' Plasma Through qPCR: A Feasible Liquid Biopsy Tool
Published on: May 27, 2016
09:38Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
Published on: June 26, 2019
Related Concept Videos
02:38Mitogens and the Cell Cycle
01:11Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase