Exosome­encapsulated microRNA­23b as a minimally invasive liquid biomarker for the prediction of recurrence and prognosis of gastric cancer patients in each tumor stage.

Recently, exosome­encapsulated microRNAs (miRNAs) have been attracting attention as stable and minimally invasive biomarkers in cancer patients. The aim of the present study was to clarify the value of plasma exosomal microRNA­23b (miR­23b) as a diagnostic and prognostic biomarker in gastric cancer (GC) patients at each tumor stage. We first selected recurrence specific exosomal miRNA by miRNA microarray from 6 GC patients (stage I) with or without recurrence, and 3 healthy volunteers. In this analysis, miR­23b demonstrated the most significant change. Subsequently, we validated the usefulness of miR­23b as a biomarker using the plasma exosome samples collected from 232 GC patients and 20 healthy volunteers. miR­23b levels were evaluated by Taqman microRNA assays. Exosomal miR­23b levels of GC patients were significantly lower than those of the healthy controls. A significant association was revealed between the plasma exosomal miR­23b levels and the expression of miR­23b in primary tumor tissues. Concerning the pathological condition, miR­23b demonstrated a significant association with tumor size, depth of invasion, liver metastasis and TNM stage. The overall survival (OS) rates of low­miR­23b patients were significantly worse than those of high­miR­23b patients at stage I, II, III and IV. The disease­free survival (DFS) rates of low exosomal miR­23b patients were significantly worse than those of high­miR­23b patients at stage I, II and III. Cox multivariate analysis indicated that exosomal miR­23b was an independent prognostic factor for OS and DFS at each tumor stage. Our results revealed that exosomal miR­23b has potential as minimally invasive predictive biomarker for the recurrence and prognosis of GC in patients at all stages.