Background
To identify specific exosomal microRNAs (miRNAs) as serum biomarkers for prediction of metastasis in patients with colorectal cancer (CRC).
Materials and Methods
Serum exosomes were isolated from patients with metastatic CRC (n = 34) and nonâmetastatic CRC (n = 108) by ultracentrifugation and characterized using transmission electron microscopy, qNano, and Western blot. Differential exosomal miRNAs were screened by sequencing and validated by qPCR in metastatic and nonâmetastatic CRC patients.
Results
After sequence analysis, KEGG analysis showed that differential genes were associated with Rap1 signaling pathway and pathways in cancer, 6 upregulated exosomal miRNAs (miRâ224â5p, miRâ548dâ5p, miRâ200aâ3p, miRâ320d, miRâ200bâ3p, and miRâ1246), and 3 downregulated exosomal miRNAs (novel_246, novel_301, and miRâ27aâ5p) were screened with fold change >1.5, among which miRâ320d was selected as the best candidate involved in CRC metastasis. Validation analysis revealed exosomal miRâ320d could significantly distinguish metastatic from nonâmetastatic CRC patients (PÂ =Â .019), with AUC of 0.633 for the diagnosis of patients with metastatic CRC. Besides, the combination of miRâ320d and CEA had an area under curve (AUC) of 0.804 for the diagnosis of patients with metastatic CRC.
Conclusion
Serum exosomal miRâ320d is a promising nonâinvasive diagnostic biomarker for distinguishing metastatic from nonâmetastatic CRC.