Tumor-derived exosomal miRNA-320d as a biomarker for metastatic colorectal cancer.

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 non-metastatic 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 non-metastatic 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 (miR-224-5p, miR-548d-5p, miR-200a-3p, miR-320d, miR-200b-3p, and miR-1246), and 3 downregulated exosomal miRNAs (novel_246, novel_301, and miR-27a-5p) were screened with fold change >1.5, among which miR-320d was selected as the best candidate involved in CRC metastasis. Validation analysis revealed exosomal miR-320d could significantly distinguish metastatic from non-metastatic CRC patients (P = .019), with AUC of 0.633 for the diagnosis of patients with metastatic CRC. Besides, the combination of miR-320d and CEA had an area under curve (AUC) of 0.804 for the diagnosis of patients with metastatic CRC. CONCLUSION:Serum exosomal miR-320d is a promising non-invasive diagnostic biomarker for distinguishing metastatic from non-metastatic CRC.

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