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Exosomal miRNA Analysis in Non-small Cell Lung Cancer (NSCLC) Patients' Plasma Through qPCR: A Feasible Liquid Biopsy Tool
Published on: May 27, 2016
AXL-mRNA Overexpression in Size-Based Enriched Circulating Tumor Cells as a Potential Biomarker for Anti-AXL Targeted
Aliki Ntzifa1, Elena Themistokli1, Areti Strati1
1Analysis of Circulating Tumor Cells Laboratory, Laboratory of Analytical Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, 15771 Athens, Greece.
Abstract:
Background: AXL, a tyrosine kinase receptor, is involved in epithelial-to-mesenchymal transition (EMT), cell survival, invasion, metastasis, and resistance to EGFR-TKIs and immune checkpoint inhibitors (ICIs). Recent clinical studies have shown promising results in NSCLC patients treated with AXL inhibitors. Methods: We evaluated AXL-mRNA overexpression in CTC fractions of NSCLC patients under osimertinib treatment (Group A, n = 39), (collected in the context of a multicenter Phase II clinical study (ClinicalTrials.gov number: NCT02771314) or immunotherapy (Group B, n = 116) at different time points collected in the context of a prospective, multicenter study (ClinicalTrials.gov number: NCT04490564). Size-based CTC enrichment (Parsortix, CelLBx Health, Guildford, UK) was used, and AXL-mRNA overexpression was evaluated using RT-qPCR. Results: In Group A, AXL-mRNA overexpression in CTC fractions was detected in 5/39 (12.8%) patients' samples at baseline, in 5/31 (16.1%) after one cycle of treatment, in 7/79 (8.9%) during treatment and in 4/32 (12.5%) at progression of disease (PD). In Group B, AXL-mRNA overexpression in CTC fractions was detected in 8/116 (6.9%) samples before immunotherapy, in 8/71 (11.3%) after three or four cycles, while no AXL transcripts were detected at PD. Conclusions: Our results indicate that AXL-mRNA overexpression in CTC fractions deserve to be further evaluated through larger clinical studies as a potential biomarker for anti-AXL targeted therapies in NSCLC.
Insights
AXL-mRNA overexpression in circulating tumor cells (CTCs) was evaluated in non-small cell lung cancer (NSCLC) patients. This biomarker warrants further study for targeted therapies in NSCLC.
Area of Science:
- Oncology
- Molecular Biology
- Biomarkers
Background:
- AXL receptor tyrosine kinase is implicated in cancer progression, metastasis, and therapeutic resistance.
- AXL signaling pathways are crucial in epithelial-to-mesenchymal transition (EMT), cell survival, and invasion.
- Emerging AXL inhibitors show promise in clinical trials for non-small cell lung cancer (NSCLC).
Purpose of the Study:
- To investigate AXL-mRNA overexpression in circulating tumor cell (CTC) fractions of NSCLC patients.
- To assess AXL-mRNA levels in patients receiving osimertinib or immunotherapy.
- To explore the potential of AXL-mRNA as a predictive biomarker for targeted therapies.
Main Methods:
- Circulating tumor cells (CTCs) were enriched using size-based methods (Parsortix).
- AXL-mRNA overexpression was quantified using reverse transcription quantitative polymerase chain reaction (RT-qPCR).
- Patient cohorts included NSCLC patients undergoing osimertinib treatment (n=39) or immunotherapy (n=116).
Main Results:
- AXL-mRNA overexpression in CTCs was detected at various time points in both treatment groups.
- In the osimertinib group, overexpression ranged from 8.9% to 16.1% across different treatment stages.
- In the immunotherapy group, overexpression was observed before and during treatment (6.9% to 11.3%), but not at disease progression.
Conclusions:
- AXL-mRNA overexpression in CTC fractions is detectable in NSCLC patients.
- These findings suggest AXL-mRNA may serve as a potential biomarker.
- Further large-scale clinical studies are warranted to validate AXL-mRNA as a biomarker for anti-AXL therapies in NSCLC.
