Correlation between the number of circulating epithelial tumor cells (CETCs/CTCs) and circulating tumor DNA (ctDNA) in patients with colorectal cancer.

Abstract

e15586 Background: The correlation between CETCs/CTCs and ctDNA has gained significant attention in cancer research, particularly in patients with colorectal cancer (CRC). Both CETCs/CTCs and ctDNA serve as non-invasive biomarkers for tumor detection, monitoring treatment response, and assessing minimal residual disease. This study aims to explore the relationship between CETCs/CTCs and ctDNA in CRC patients and evaluate their potential as complementary diagnostic and prognostic tools. Furthermore, we assess the feasibility of detecting KRAS mutations in individually picked CETCs to demonstrate the heterogeneity within a single patient. Methods: Blood samples were collected from CRC patients at various stages of the disease. The number of CETCs/CTCs was analyzed using the maintrac method, while ctDNA was assessed with the cobas KRAS mutation test. Additionally, for patients with a sufficient number of CETCs, 10 CETCs/CTCs from each patient were individually isolated using a semi-automated capillary technique and deposited one by one into micro cups. The DNA of each individual cell was then amplified using whole genome amplification and analyzed with the cobas® KRAS mutation test. Results: The results demonstrate a correlation between the presence and quantity of CETCs/CTCs and ctDNA levels, suggesting that both biomarkers reflect the underlying tumor biology and disease progression. During long-term observation, an increase in ctDNA was observed alongside a rise in CETCs. Regarding the analysis of KRAS mutations in single CETC/CTC cells, DNA was successfully amplified from all individually isolated cells. A KRAS mutation was detected in 20–75% of evaluable cells in patients with a KRAS mutation in the primary tumor. Conclusions: This study highlights a significant correlation between CETCs/CTCs and ctDNA in CRC patients, indicating their potential as complementary biomarkers for tumor monitoring and disease progression. The detection of KRAS mutations in individual CETCs underscores the heterogeneity within patients. These findings suggest that combining CETCs and ctDNA could enhance personalized treatment strategies and improve CRC management in the future.