Overexpression of serum extracellular vesicle microRNA-215-5p is associated with early tumor recurrence and poor prognosis of gastric cancer

Abstract

Objectives: Extracellular vesicle microRNAs (EV-miRNAs) have been demonstrated to be reliable candidate biomarkers for clinical applications. However, the clinical application potential of serum EV-miR-215-5p for gastric cancer (GC) remains poorly understood. The goal of our study was to determine the efficacy of serum EV-miR-215-5p in predicting the prognosis of GC.

Methods: Blood samples were collected from 118 patients with GC, 60 patients with benign gastric disease and BGD and 70 healthy controls. The relative levels of serum EV-miR-215-5p were measured using quantitative real-time polymerase chain reaction (qRT-PCR).

Results: Compared to patients with BGD and normal controls, GC patients exhibited remarkably higher serum EV-miR-215-5p level, especially those with early tumor recurrence (ETR). Receiver operating characteristic (ROC) curve analysis showed that serum EV-miR-215-5p was able to distinguish GC patients from BGD patients or healthy controls and GC patients with ETR from those without ETR. In addition, increased serum EV-miR-215-5p levels were notably correlated with invasive depth, TNM stage, and lymph node metastasis. Moreover, serum EV-miR-215-5p levels were greatly decreased after surgical treatment, but increased at the time of ETR. Survival analysis showed that patients with higher serum EV-miR-215-5p had shorter survival. Furthermore, serum EV-miR-215-5p was an independent risk factor for GC.

Conclusions: Serum EV-miR-215-5p might be a novel biomarker for predicting ETR and prognosis of GC.

Figure 1. Serum EV-miR-215-5p level was higher in GC patients. (A) The isolated extracellular vesicles were positive for TSG-101 and CD9. (B) Serum extracellular vesicle miR-215-5p levels were markedly higher in GC patients than those in BGD patients and healthy subjects. (C) Serum extracellular vesicle miR-215-5p levels were higher in patients with ETR than in those without ETR.

Figure 2. The diagnostic performance of serum EV-miR-215-5p. (A) The diagnostic performance of serum EV-miR-215-5p for distinguishing GC patients from healthy donors. (B) The diagnostic performance of serum EV-miR-215-5p for distinguishing GC patients from BGD patients. (C) The diagnostic performance of serum EV-miR-215-5p for identifying GC patients with ETR from those without ETR.

Figure 3. The serum EV-miR-215-5p level was sensitive to treatments. (A) Serum EV-miR-215-5p level was significantly decreased in GC patients without ETR after gastrectomy. (B) The serum EV-miR-215-5p level was decreased in GC patients with ETR after gastrectomy but increased at the point of ETR.

Figure 4. Correlation between serum EV-miR-215-5p level and OS and DFS. (A) GC patients with high serum EV-miR-215-5p levels had shorter OS. (B) GC patients with higher serum EV-miR-215-5p levels had worse DFS.