Reduced expression of exosomal miR‑29s in peritoneal fluid is a useful predictor of peritoneal recurrence after curative resection of gastric cancer with serosal involvement

Abstract

The peritoneal surface is the most frequent site of metastasis disease in patients with gastric cancer. Even after curative surgery and adjuvant chemotherapy, peritoneal recurrences often develop. Exosomes play pivotal roles in tumor metastasis via the transfer of microRNAs (miRNAs). In the present study, exosomes were isolated from peritoneal lavage fluid or ascites in 85 patients with gastric cancer and the relative expression levels of miR-29s were examined. The expression of miR-29a-3p, miR-29b-3p and miR-29c-3p in peritoneal exosomes were all downregulated in patients with peritoneal metastases (PM) compared to those without PM. In 30 patients who underwent curative gastrectomy with serosa-involved (T4) gastric cancer, 6 patients exhibited recurrence in the peritoneum within 12 months. The expression levels of miR-29s at gastrectomy tended to be lower in these 6 patients than in the other 24 patients with significant differences in miR-29b-3p (P=0.003). When the patients were divided into two groups based on median levels of miR-29s, peritoneal recurrence developed more frequently in patients with low expression of miR-29b-3p, and lower expression of miR-29s were related with worse overall survival. miR-29s are thought to play a suppressive role in the growth of disseminated peritoneal tumor cells. Reduced expression of miR-29b in peritoneal exosomes is a strong risk factor of developing postoperative peritoneal recurrence.

miR-181a, delivered by hypoxic PTC-secreted exosomes, inhibits DACT2 by downregulating MLL3, leading to YAP-VEGF-mediated angiogenesis

“… 24 EXs can shuttle their cargos of proteins, mRNAs, and miRNAs between cells, and EXs secreted from cancer cells can have effects on the tumor microenvironment. 25 In the current study, the obtained findings revealed that exosomal miR-181a from hypoxia-induced PTC cells enhanced angiogenesis and tumor growth by downregulation of MLL3 and DACT2 and upregulation of YAP and VEGF signaling.…”

Gastric Cancer: Advances in Carcinogenesis Research and New Therapeutic Strategies

“…Studies show that miRNA can be identified in serum-circulating exosomes, allowing the staging of patients. For example, exosomes containing miR-29s are found to play a suppressive role in the growth of peritoneal-disseminated tumour cells and are under-expressed in patients with peritoneal metastases [ 115 ]. Low expression of this miRNA in exosomes is correlated to bad prognosis of patients.…”

Predicting Peritoneal Dissemination of Gastric Cancer in the Era of Precision Medicine: Molecular Characterization and Biomarkers

“…Research advances in GC-derived peritoneal exosomes have involved the examination of exosomal biomarkers in peritoneal fluid. Recently, reduced expression of exosomal miR-29s were found to be associated with synchronous PD and PD recurrence in GC with serosal involvement [127].…”