AR4 - Exosomal microRNA in Peritoneal Fluid as a Biomarker of Peritoneal Metastases from Gastric Cancer

Peritoneal metastases (PM) frequently occur and result in a poor prognosis for patients with gastric cancer. Exosomes play pivotal roles in tumor metastasis via the transfer of microRNAs (miRNAs). We examined the exosomal miRNA profile in peritoneal fluids to identify to novel biomarkers to reflect the tumor burden on peritoneum.Exosomes were isolated from peritoneal fluids of patients of gastric cancer with macroscopic (P1) or microscopic (P0CY1) peritoneal metastasis (PM) and comprehensive miRNA expression analysis was performed. Then, the expressions of candidate miRNAs were validated in all 58 samples using TaqMan Advanced miRNA Assays.In initial screening, we performed comprehensive analysis of exosomal miRNA using 11 and 14 peritoneal fluids with or without PM, respectively, and identified 11 dysregulated miRNAs in PM (+) samples. Validation analysis revealed that 4 miRNAs (miR-21-5p, miR-92a-3p, miR-223-3p, and miR-342-3p) were significantly upregulated in 12 PM (+) samples, and their expression levels showed positive correlation with peritoneal cancer index (PCI). In contrast, miR-29 family were all downregulated in patients with PM (+) samples. Moreover, in 24 patients with pT4 tumor, miR-29s at gastrectomy tended to be lower in 6 patients with peritoneal recurrence with significant differences in miR-29b-3p (p=0.012). Expression pattern of miRNAs in peritoneal exosome well reflects the tumor burden in peritoneal cavity and could be useful biomarker in the treatment of PM. MiR-29s are thought to play a suppressive role in the growth of disseminated peritoneal tumor cells and could be a novel nucleic acid medicine for the prevention of peritoneal recurrence.