Extrachromosomal circular DNA as a novel biomarker for the progression of colorectal cancer

Abstract

Background: Extrachromosomal circular DNA (eccDNA) has potential in tumor diagnosis, particularly for improving diagnostic accuracy and early cancer detection; however, many challenges remain in its application to clinical practice. Methods: We conducted a Circle‐Seq analysis on clinical samples at different stages of colorectal cancer progression to examine the dynamic changes of eccDNA during the progression of colorectal cancer. We used breakpoint-specific PCR to verify candidate eccDNAs identified by Circle‐Seq. The results were further validated using the AOM/DSS-induced colorectal cancer model. Results: There was an increase in the abundance of eccDNA with the progression of colorectal cancer. The genes associated with these eccDNA molecules were primarily related to signaling pathways involved in tumor development and metastasis. Our analysis also revealed that eccDNA abundance positively correlates with gene expression, and eccDNA derived from specific genes has potential value for the early diagnosis of tumors. Conclusions: This study revealed a connection between eccDNA and colorectal cancer progression and highlights the clinical potential of eccDNA for the early diagnosis of colorectal cancer.