MicroRNAs associated with postoperative outcomes in patients with limited stage neuroendocrine carcinoma of the esophagus

Esophageal neuroendocrine carcinoma (E‑NEC) is an aggressive disease with a poor prognosis. The present study aimed to assess the role of surgery in the treatment of patients with resectable E‑NEC, and identify a microRNA (miRNA/miR) signature in association with positive postoperative outcomes. Between February 2017 and August 2019, 36 patients with E‑NEC who underwent curative surgery at the Japan Neuroendocrine Tumor Society partner hospitals were enrolled in the study. A total of 16 (44.4%) patients achieved disease‑free survival (non‑relapse group), whereas 20 (55.6%) patients developed tumor relapse (relapse group) during the median follow‑up time of 36.5 months (range, 1‑242) after surgery with a 5‑year overall survival rate of 100 and 10.8%, respectively (P<0.01). No clinicopathological parameters, such as histological type or TNM staging, were associated with tumor relapse. Microarray analysis of 2,630 miRNAs in 11 patients with sufficient quality RNA revealed 12 miRNAs (miR‑1260a, ‑1260b, ‑1246, ‑4284, ‑612, ‑1249‑3p, ‑296‑5p, ‑575, ‑6805‑3p, ‑12136, ‑6822‑5p and ‑4454) that were differentially expressed between the relapse (n=6) and non‑relapse (n=5) groups. Furthermore, the top three miRNAs (miR‑1246, ‑1260a and ‑1260b) were associated with overall survival (P<0.01). These results demonstrated that surgery‑based multidisciplinary treatment is effective in a distinct subpopulation of limited stage E‑NEC. A specific miRNA gene set is suggested to be associated with treatment outcome.