New Aptamer-Based Liquid Biopsy Offers Prognostic Insight in Lung Cancer

A new study published in Cancers introduces a promising alternative to conventional circulating tumor cell (CTC) detection for non-small cell lung cancer (NSCLC), using DNA aptamers to overcome the limitations of traditional epithelial marker-based methods.

Researchers developed and validated two synthetic DNA aptamers, LC-17 and LC-18, which target proteins expressed by lung cancer cells, including those undergoing epithelial-to-mesenchymal transition—a major obstacle for EpCAM-dependent detection systems. These aptamers were tested in a cohort of 43 NSCLC patients, offering a non-invasive approach for detecting CTCs in peripheral blood.

Using mass spectrometry, the study identified neutrophil defensin 1 and peroxiredoxin-2 as the primary binding targets of the LC-17 aptamer. Neither of these proteins was detected in healthy donor blood samples, suggesting their specificity for tumor-derived cells. These proteins are associated with tumor immunity and oxidative stress regulation—two biological processes linked to cancer progression and poor prognosis.

The aptamer-based assay proved sensitive in detecting CTCs across varying stages of lung cancer. Importantly, the number of aptamer-positive CTCs showed a statistically significant correlation with both tumor size and lymph node involvement. Patients with advanced primary tumors (T4) had higher CTC counts than those with smaller tumors (T1–T3; p = 0.012), and those with mediastinal lymph node metastasis (N2) exhibited elevated CTC levels compared to N0–N1 groups (p = 0.014).

Perhaps most compellingly, elevated CTC counts (>2 cells/4 mL of blood) were associated with worse overall survival. Patients with high CTC levels had a median survival of 15 months compared to 33 months for those with lower counts (p = 0.044), suggesting prognostic utility for this method.

The authors propose integrating this aptamer-based technique into standard clinical workflows for NSCLC. Unlike traditional antibody-based platforms, aptamers offer advantages such as greater stability, specificity, and the ability to bind a wider range of biomarkers. They are also smaller and synthetically produced, reducing variability between batches.

However, the study acknowledges the need for larger, multi-center trials to establish standardized CTC thresholds and validate clinical utility. Further investigation into the three-dimensional structure and binding epitopes of the aptamers is also planned to improve specificity and reduce potential cross-reactivity.

This aptamer-based assay, by capturing tumor cell heterogeneity and providing prognostic insight, may represent a meaningful step toward more personalized and less invasive monitoring of lung cancer.