Related Experiment Video
Updated: Aug 16, 2025
Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
Published on: June 26, 2019
Comprehensive Analysis of Circular RNA Expression Profiles in Gefitinib-Resistant Lung Adenocarcinoma Patients
Junyong Zou1,2,3, Huiyin Lan4,5,6, Wei Li1
1Department of Respiratory Medicine, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai, China.
Abstract:
Introduction: Gefitinib is a selective epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) widely used in lung adenocarcinoma (LUAD) patients harboring sensitive EGFR mutations. Although it has a good initial efficacy, acquired resistance to gefitinib is eventually inevitable. Studies have shown that circular RNA (circRNA) is involved in the development of acquired resistance to different anti-cancer drugs, but the comprehensive analysis of its expression profile and functions on acquired gefitinib resistance remains poor. Methods: To explore the aberrant circRNAs expression profiles, we collected peripheral plasma samples from 4 gefitinib-sensitive and 4 gefitinib-resistant patients for performing microarray analysis. Candidates of differentially expressed circRNAs were used and analyzed by bioinformatics modalities including gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and a constructed circRNA-microRNA RNA network. The differential expression of selected circRNAs was verified by quantitative real-time PCR (qRT-PCR). Results: A total of 2571 circRNAs with significantly different expression between the groups were identified by microarray analysis. GO, KEGG, and pathway enrichment analyses reveal that these differentially expressed circRNAs (DECs) were complicated in many biological pathways that may be related to EGFR-TKI resistance such as ABC transporter and PI3K-Akt pathways. A circRNA-microRNA network was constructed by 10 circRNAs potentially involved in EGFR-TKI resistance togethering with their corresponding microRNAs (miRNAs). Consistent with the results of microarray assay, hsa_circ_0030591 and hsa_circ_0040348 were validated to be upregulated in gefitinib-resistant patients by qRT-PCR. Conclusions: Our study provides valuable data on circRNAs expression profiles detected in liquid biopsy for LUAD patients with acquired gefitinib resistance, and we validate that upregulations of hsa_circ_0030591 and hsa_circ_0040348 may play key roles in EGFR-TKI resistance and thus serving as candidates for biomarker.
Insights
Circular RNAs (circRNAs) in liquid biopsies show altered expression in lung adenocarcinoma patients resistant to gefitinib (EGFR-TKI). Upregulated circRNAs like hsa_circ_0030591 may indicate acquired resistance.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Gefitinib, an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), is a key treatment for lung adenocarcinoma (LUAD) with EGFR mutations.
- Acquired resistance to gefitinib is a significant clinical challenge, limiting long-term patient outcomes.
- Circular RNAs (circRNAs) are implicated in drug resistance, but their role in gefitinib resistance in LUAD requires comprehensive investigation.
Purpose of the Study:
- To comprehensively analyze the expression profile of circRNAs in LUAD patients who developed acquired resistance to gefitinib.
- To identify specific circRNAs and their associated pathways involved in gefitinib resistance.
- To explore the potential of circRNAs as biomarkers for acquired gefitinib resistance.
Main Methods:
- Microarray analysis of circRNA expression profiles in plasma samples from gefitinib-sensitive and resistant LUAD patients.
- Bioinformatic analyses including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and circRNA-microRNA network construction.
- Validation of differentially expressed circRNAs using quantitative real-time PCR (qRT-PCR).
Main Results:
- Microarray analysis identified 2571 differentially expressed circRNAs (DECs) between sensitive and resistant groups.
- Pathway enrichment analyses indicated involvement of DECs in pathways relevant to EGFR-TKI resistance, such as ABC transporter and PI3K-Akt signaling.
- A circRNA-microRNA network highlighted 10 circRNAs potentially involved in resistance; hsa_circ_0030591 and hsa_circ_0040348 were validated as upregulated in resistant patients.
Conclusions:
- This study provides the first comprehensive circRNA expression profile in liquid biopsies of LUAD patients with acquired gefitinib resistance.
- Upregulation of hsa_circ_0030591 and hsa_circ_0040348 may play critical roles in the development of EGFR-TKI resistance.
- These identified circRNAs show promise as potential biomarkers for predicting or monitoring acquired gefitinib resistance in LUAD.
More Related Videos
09:38Establishing 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
13:34A Combined 3D Tissue Engineered In Vitro/In Silico Lung Tumor Model for Predicting Drug Effectiveness in Specific Mutational Backgrounds
Published on: April 6, 2016