Circulating miR-18a in plasma contributes to cancer detection and monitoring in patients with gastric cancer

Recently, circulating microRNAs have been reported to be stably detectable in plasma/serum and to function as potent non-invasive biomarkers in various cancers. We hypothesized that miR-18a could contribute to a novel plasma biomarker in patients with gastric cancer (GC). We focused on miR-18a, which is a component of miR-17-92 cluster and has been reported as highly expressed in GC tissues. The study involved three steps: (1) confirmation of the higher miR-18a expression in primary GC tissues and GC cell lines than in normal gastric tissues and a fibroblast cell line; (2) evaluation of the plasma miR-18a assay using quantitative RT-PCR by comparing 104 GC patients and 65 healthy volunteers; (3) evaluation of monitoring tumor dynamics by the plasma miR-18a assay. (1) The miR-18a expressions were significantly higher in GC tissues than in normal gastric tissues (P = 0.0286) and higher in all examined GC cell lines than in the fibroblast cell line. (2) The plasma miR-18a concentrations were significantly higher in GC patients than in healthy controls (P < 0.0001). The value of the area under the receiver-operating characteristic curve was 0.8059. (3) The plasma miR-18a levels were significantly reduced in postoperative samples compared to in preoperative samples (P = 0.0002). In an miR-18a overexpressing cell line, the miR-18a concentration of cultured medium increased in both cell number and time-course dependent manners, suggesting microRNA might be released from cancer cells into the surrounding environment. Circulating miR-18a could be a useful biomarker for screening GC and monitoring tumor dynamics.