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

Abstract

BackgroundTo identify specific exosomal microRNAs (miRNAs) as serum biomarkers for prediction of metastasis in patients with colorectal cancer (CRC).Materials and MethodsSerum 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.ResultsAfter 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.ConclusionSerum exosomal miR‐320d is a promising non‐invasive diagnostic biomarker for distinguishing metastatic from non‐metastatic CRC.