Abstract

Background. Increasing evidence suggests that exosomal circular RNAs (circRNAs) could serve as promising novel biomarkers for colorectal cancer (CRC) detection. However, diagnostic potential of exosomal circRNAs in CRC metastasis remain largely underexplored. Methods. The differentially expressed circRNAs (DEcircRNAs) were screened through GSE159669 and GSE205643 datasets. Seventy patients with CRC and seventy age- and sex-matched healthy controls were retrospectively enrolled in this study. The expression of DEcircRNAs was validated in paired cancer and paracancerous tissues, as well as in serum and serum-derived exosomes by RT-qPCR. The clinical significance, prognostic, and diagnostic efficacy of DEcircRNAs were evaluated through chi-square test, Kaplan-Meier survival curves, Cox regression model analysis, and receiver operating characteristic curves. The effect of DEcircRNAs on CRC cell migration and invasion was assessed through wound healing and transwell assays with gain- and loss-of-function methods. Results. A total of six DEcircRNAs were identified, among which only hsa_circ_0005692 exhibited consistent upregulation in cancer tissues, serum, and serum-derived exosomes from patients with CRC. Increased exosomal hsa_circ_0005692 was positively associated with lymph node metastasis and distant metastasis. Patients with elevated levels of exosomal hsa_circ_0005692 exhibited lower overall survival and progression-free survival rates, and exosomal hsa_circ_0005692 was identified as an independent risk factor for poor overall survival. Notably, exosomal hsa_circ_0005692 showed superior diagnostic accuracy than its expression in tissues and serum counterparts in differentiating not only CRC patients from healthy controls, but also metastatic patients from non-metastatic patients. Moreover, hsa_circ_0005692 was found to facilitate CRC metastasis by promoting cell migration and invasion as well as epithelial-mesenchymal transition. Conclusion. This study provides p