Targeting CTC Heterogeneity: Aptamer-Based Liquid Biopsy Predicts Outcome in Lung Cancer

Area of Science:

• Biotechnology
• Oncology
• Molecular Diagnostics

Background:

• Circulating tumor cells (CTCs) are crucial for lung cancer (LC) diagnosis and monitoring.
• Current CTC detection methods face limitations due to tumor cell heterogeneity and reliance on markers like EpCAM.
• DNA aptamers offer high specificity, stability, and versatility for targeting diverse cancer biomarkers.

Purpose of the Study:

• To develop and validate a DNA aptamer-based liquid biopsy for isolating and detecting CTCs in non-small cell lung cancer (NSCLC).
• To identify protein targets of aptamers used for CTC detection.
• To assess the correlation between CTC counts and clinical parameters, including tumor stage, metastasis, and patient survival.

Main Methods:

• Utilized DNA aptamers LC-17 and LC-18, selected against primary lung tumor tissue, for CTC isolation.
• Employed liquid chromatography-mass spectrometry (LC-MS/MS) to identify protein targets of aptamer LC-17.
• Isolated CTCs from NSCLC patients' blood via filtration and detected them using fluorescence microscopy with FAM-labeled aptamers.

Main Results:

• Aptamer LC-17 identified neutrophil defensin 1 (DEFA1) and peroxiredoxin-2 (PRDX2) as key CTC protein targets, absent in healthy donors.
• Elevated CTC counts (>3 cells/4 mL blood) significantly correlated with advanced tumor size (T4), extensive lymph node metastasis (N3), and reduced overall survival.
• The aptamer method demonstrated effectiveness in capturing heterogeneous CTC populations, independent of EpCAM expression.

Conclusions:

• The developed aptamer-based liquid biopsy is an effective, non-invasive tool for detecting CTCs in NSCLC patients.
• CTC counts derived from this method serve as a relevant prognostic biomarker, correlating strongly with disease progression and survival.
• This approach holds potential for clinical integration in NSCLC monitoring and patient stratification.