Molecular profile of exosomal miRNA differential expression in ascites of untreated advanced gastric cancer patients with peritoneal metastases.

Abstract

e16086 Background: The incidence of gastric cancer is high, and the proportion of peritoneal metastases among patients with early-stage operable gastric cancer is about 10%-20%, while the proportion of peritoneal metastases among patients with stage 3 (stage III) gastric cancer is as high as 40%. The prognosis of gastric cancer patients with peritoneal metastases is poor, with a median survival of 7 months. Exosomes are considered to be carriers of intercellular communication and abundant miRNAs (miRNAs) are enriched in patients' ascitic fluid exosomes. Methods: Ascites exosomes were characterized according to ISEV2018. The pro-tumor proliferation and metastatic ability of ascites exosomes in gastric cancer patients with peritoneal metastases was observed by small animal in vivo imaging. Six untreated ascites exosomes from gastric cancer patients with peritoneal metastases were selected for miRNA sequencing with five ascites exosomes from patients with benign disease to determine differentially expressed molecular profiles. The target mRNAs of selected miRNAs were predicted by miRhybrid, TargetScan database, and enriched in KEGG database for the function of target mRNAs. Results: Compared to ascites exosomes from patients with benign disease, or ascites exosomes removed from gastric cancer patients with peritoneal metastases, ascites exosomes from gastric cancer patients with peritoneal metastases had a significant contribution to tumor proliferation and metastasis. Among them, molecules such as miR-196 were expressed up-regulated in all six samples of gastric cancer peritoneal metastasis group, and the difference was significant. The target mRNAs of differentially expressed miRNAs were associated with motility, adhesion, stromal degradation, hypoxia tolerance, apoptosis, and angiogenesis (biological behaviors involved in this process of gastric cancer peritoneal metastasis). Conclusions: Molecules such as miR-196 are important for the clinical problem of peritoneal metastasis of gastric cancer and can be used as biomarkers for disease assessment and potential therapeutic target.