Exosomal miR-30b-3p and miR-99a-5p as potential biomarkers for distinguishing primary and metastatic colon cancer

Abstract Objectives Colon cancer (CC) remains one of the leading causes of cancer-related mortality worldwide, and reliable non-invasive biomarkers for disease staging and monitoring are still lacking. Exosomal microRNAs (miRNAs) have emerged as promising candidates for liquid biopsies due to their stability and tumor-specific expression profiles. This pilot study evaluated the diagnostic potential of four serum exosomal miRNAs, miR-30b-3p, miR-99a-5p, miR-769-5p, and miR-3937, in differentiating CC patients (n=28) from healthy controls (n=20), and primary (n=24) from metastatic tumors (n=4). Methods Exosomal RNA was isolated and quantified using digital polymerase chain reaction (dPCR). Results miR-30b-3p and miR-3937 were upregulated in patients vs. controls, while miR-30b-3p showed a striking 67.8-fold higher expression in primary compared with metastatic tumors (AUC=0.771). Conversely, miR-99a-5p was elevated 5.4-fold in metastatic tumors. Combined miRNA panels improved performance, with the miR-30b-3p/miR-99a-5p/miR-3937 panel achieving an AUC of 0.932, suggesting synergistic diagnostic value. Conclusions This study provides preliminary evidence supporting exosomal miR-30b-3p as a potential liquid biopsy biomarker for stage-specific detection of CC, warranting validation in larger cohorts.