Recently, exosome‑encapsulated 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 microRNA‑23b (miR‑23b) 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, miR‑23b demonstrated the most significant change. Subsequently, we validated the usefulness of miR‑23b as a biomarker using the plasma exosome samples collected from 232 GC patients and 20 healthy volunteers. miR‑23b levels were evaluated by Taqman microRNA assays. Exosomal miR‑23b levels of GC patients were significantly lower than those of the healthy controls. A significant association was revealed between the plasma exosomal miR‑23b levels and the expression of miR‑23b in primary tumor tissues. Concerning the pathological condition, miR‑23b demonstrated a significant association with tumor size, depth of invasion, liver metastasis and TNM stage. The overall survival (OS) rates of low‑miR‑23b patients were significantly worse than those of high‑miR‑23b patients at stage I, II, III and IV. The disease‑free survival (DFS) rates of low exosomal miR‑23b patients were significantly worse than those of high‑miR‑23b patients at stage I, II and III. Cox multivariate analysis indicated that exosomal miR‑23b was an independent prognostic factor for OS and DFS at each tumor stage. Our results revealed that exosomal miR‑23b has potential as minimally invasive predictive biomarker for the recurrence and prognosis of GC in patients at all stages.

In patients with gastric cancer (GC), peritoneal recurrence is a common risk and associated with poor prognosis. A novel biomarker for the prediction of high-risk peritoneal recurrence in patients with GC is desirable. The present study investigated the effectiveness of exosome-encapsulated microRNAs (ex-miRNAs) as minimally invasive biomarkers in patients with GC that received curative surgery. Recurrence-specific ex-miRNAs were selected following comparison of miRNA microarray data from patients with TNM stage II GC with peritoneal recurrence (n=3) and without peritoneal recurrence following curative surgery (n=3), and three healthy volunteers. In this analysis, exosome-encapsulated miRNA-21 (ex-miR-21) and exosomal miR-92a (ex-miR-92a) exhibited the greatest alterations in expression patterns. Using plasma exosome samples collected from another 129 patients with stage II and III GC, the present study investigated the potential value of ex-miR-21 and ex-miR-92a as biomarkers. Ex-miRNA levels were measured using TaqMan miRNA assays. Ex-miR-21 levels were significantly higher and ex-miR-92a levels were significantly lower in samples from patients with GC compared with healthy controls. The overall survival (OS) and peritoneal recurrence-free survival (PRFS) were poorer in stage II and III patients with high ex-miR-21 levels than in patients with low miR-21 levels. OS and PRFS of stage II and III patients with low ex-miR92a levels were significantly worse than those with high ex-miR92a levels. Cox multivariate analyses indicated that ex-miR-21 and ex-miR-92a were independent prognostic factors for OS and PRFS in stage II and III GC. A negative correlation was detected between expression levels of miR-21 and programmed cell death protein 4 mRNA, and miR-92a and prostaglandin E receptor 4 mRNA. Therefore, ex-miR-21 and ex-miR-92a may function as effective and minimally invasive biomarkers for the prediction of peritoneal recurrence and the prognosis of patients with stage II/III GC.

The formula of Cockcroft and Gault is the best predictive equation of creatinine clearance, except in the extremely elderly women.

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