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Updated: Oct 24, 2025
Exosomal miRNA Analysis in Non-small Cell Lung Cancer NSCLC Patients' Plasma Through qPCR: A Feasible Liquid Biopsy Tool
Published on: May 27, 2016
Liquid biopsy uncovers distinct patterns of DNA methylation and copy number changes in NSCLC patients with different
Hoai-Nghia Nguyen1, Ngoc-Phuong Thi Cao2, Thien-Chi Van Nguyen2
1University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam. nhnghia81@gmail.com.
Abstract:
Targeted therapy with tyrosine kinase inhibitors (TKI) provides survival benefits to a majority of patients with non-small cell lung cancer (NSCLC). However, resistance to TKI almost always develops after treatment. Although genetic and epigenetic alterations have each been shown to drive resistance to TKI in cell line models, clinical evidence for their contribution in the acquisition of resistance remains limited. Here, we employed liquid biopsy for simultaneous analysis of genetic and epigenetic changes in 122 Vietnamese NSCLC patients undergoing TKI therapy and displaying acquired resistance. We detected multiple profiles of resistance mutations in 51 patients (41.8%). Of those, genetic alterations in EGFR, particularly EGFR amplification (n = 6), showed pronounced genome instability and genome-wide hypomethylation. Interestingly, the level of hypomethylation was associated with the duration of response to TKI treatment. We also detected hypermethylation in regulatory regions of Homeobox genes which are known to be involved in tumor differentiation. In contrast, such changes were not observed in cases with MET (n = 4) and HER2 (n = 4) amplification. Thus, our study showed that liquid biopsy could provide important insights into the heterogeneity of TKI resistance mechanisms in NSCLC patients, providing essential information for prediction of resistance and selection of subsequent treatment.
Insights
Liquid biopsy reveals genetic and epigenetic changes driving tyrosine kinase inhibitor (TKI) resistance in non-small cell lung cancer (NSCLC). Hypomethylation linked to EGFR amplification correlates with treatment duration, aiding resistance prediction.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Targeted therapy with tyrosine kinase inhibitors (TKI) improves survival in non-small cell lung cancer (NSCLC).
- Acquired resistance to TKI is a significant clinical challenge, limiting long-term patient benefit.
- Mechanisms of TKI resistance, particularly in clinical settings, require further elucidation.
Purpose of the Study:
- To investigate the genetic and epigenetic alterations underlying TKI resistance in NSCLC patients using liquid biopsy.
- To explore the association between specific genetic changes, epigenetic modifications, and clinical response duration.
Main Methods:
- Simultaneous analysis of genetic and epigenetic changes via liquid biopsy in 122 Vietnamese NSCLC patients with acquired TKI resistance.
- Detection and profiling of resistance mutations, including EGFR, MET, and HER2 amplification.
- Assessment of genome-wide methylation status and its correlation with clinical parameters.
Main Results:
- Resistance mutations were identified in 41.8% of patients.
- EGFR amplification was associated with genome-wide hypomethylation and pronounced genome instability.
- Hypomethylation levels correlated with the duration of response to TKI treatment.
- Hypermethylation in Homeobox gene regulatory regions was observed, but not with MET or HER2 amplification.
Conclusions:
- Liquid biopsy is a valuable tool for understanding the heterogeneity of TKI resistance mechanisms in NSCLC.
- Specific epigenetic changes, like hypomethylation, may serve as biomarkers for predicting TKI resistance and guiding subsequent treatment strategies.
- Distinct genetic profiles (e.g., EGFR amplification vs. MET/HER2 amplification) are associated with different resistance mechanisms.
