Prognostic impact of circulating miR-21 and miR-375 in plasma of patients with esophageal squamous cell carcinoma

Background: miR-21 and miR-375 are reported to be highly and poorly expressed in esophageal squamous cell carcinoma (ESCC) tissues, respectively. Recently, we demonstrated that circulating miR-21 and miR-375 were stably detectable in plasma and reflected tumor dynamics as a tumor marker for ESCC. We hypothesized that these plasma miRNA concentrations contributed to prognostic markers in patients with ESCC. Methods: Between 2008 and 2010, 50 preoperative plasma samples were collected from consecutive patients with ESCC, who underwent curative esophagectomy in our hospital. We examined the association between plasma miRNA concentrations and prognosis retrospectively. Results: i) The postoperative cause-specific survival rate of patients with high plasma miR-21 concentration tended to be poorer than low group (3-yr survival rate: 53.4 and 81.5%, p = 0.1038), while that of high plasma miR-375 group was better than low group (3-yr survival rate: 100 and 65.2%). ii) Patients with high miR-21 and low miR-375 concentrations in plasma had significantly poorer prognosis than other patients (3-yr survival rate: 48.4 and 83.1%, p = 0.039). Multivariate analysis revealed that the presence of high miR-21 and low miR-375 concentrations in plasma was an independent prognostic factor (p = 0.029, hazard ratio 3.8 (1.14-12.5)). Conclusion: Circulating miR-21 and miR-375 could be reliable prognostic markers for ESCC. These plasma markers might facilitate clinical decision-making to select prospective candidates, which need meticulous follow-up for early detection of recurrences and additional treatments such as neo-adjuvant chemotherapy and postoperative chemotherapy in ESCC.