Clinical impact of circulating miR-18a in plasma of patients with oesophageal squamous cell carcinoma

Background: Several recent studies demonstrated that microRNAs are stably detectable in plasma/serum. We tested whether miR-18a, which is located in the miR-17-92 cluster and reported to be highly expressed in tissues of oesophageal squamous cell carcinoma (ESCC), served as a plasma biomarker in patients with ESCC. Methods: This study was divided into three steps: (1) confirmation of higher miR-18a levels in primary ESCC tissues and cell lines than normal ESCC tissues and a human fibroblast cell line. (2) Evaluation of the plasma miR-18a assay using quantitative RT-PCR by comparing results from 106 consecutive patients with ESCC and 54 healthy volunteers. (3) Evaluation of the assay for monitoring tumour dynamics in patients with ESCC. Results: (1) Expression of miR-18a was significantly higher in ESCC tissues (P = 0.0020) and ESCC cell lines (P = 0.0121) than normal tissues and fibroblasts. (2) Plasma concentrations of miR-18a were significantly higher in ESCC patients than healthy volunteers (P < 0.0001; ESCC patients vs healthy volunteers (mean +/- s.d.): 11.77 +/- 13.45 vs 0.73 +/- 0.54 amol mu l(-1)). The value of the area under the receiver-operating characteristic (ROC) curve (AUC) was 0.9449. Furthermore, the ROC curves to detect early ESCC such as pTis-1 and pStage0-1 showed AUCs of 0.9479 and 0.9642, respectively. (3) Plasma levels of miR-18a were significantly lower in postoperative samples than preoperative samples (P = 0.0076). Conclusion: Plasma miR-18a may be a very useful biomarker for cancer detection and the monitoring of tumour dynamics in patients with ESCC.