Exosomal microRNA in peritoneal fluid as a biomarker of peritoneal metastases from gastric cancer

Abstract

Aim: Peritoneal metastases (PM) frequently occur in patients with gastric cancer and result in a poor prognosis. Exosomes play pivotal roles in tumor metastasis through the transfer of microRNAs (miRNAs). We examined the exosomal miRNA profile in peritoneal fluids to identify novel biomarkers to reflect tumor burden in the peritoneum. Methods: 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 carried out. Expressions of candidate miRNAs were then validated in all 58 samples using TaqMan Advanced miRNA Assays. Results: In initial screening, we carried out comprehensive analysis of exosomal miRNA using peritoneal fluids from 11 and 14 patients with or without PM, respectively, and identified 11 dysregulated miRNAs in PM (+) samples. Validation analysis showed that four 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. In contrast, miR-29 family were all downregulated in patients with PM (+) samples. Moreover, in 24 patients with pT4 tumor, miR-29 at gastrectomy tended to be lower in six patients with peritoneal recurrence with significant differences in miR-29b-3p (P = .012). Conclusion: Expression pattern of miRNAs in peritoneal exosomes well reflects the tumor burden in the peritoneal cavity and could be a useful biomarker in the treatment of PM. K E Y W O R D S biomarker, exosome, intraperitoneal chemotherapy, microRNA, peritoneal metastasis | 85 OHZAWA et Al.

The roles of extracellular vesicles in the development, microenvironment, anticancer drug resistance, and therapy of head and neck squamous cell carcinoma

“…Theodoraki et al demonstrated that CD44v3 protein-carrying TDE are correlated with higher disease stages and lymph node metastasis; thus, TDE could potentially serve as a noninvasive biomarker of cancer progression [65]. Studies have shown that ubiquitin C-terminal hydrolase L1 (UCH-L1) promotes motility of metastatic HNSCC as well as of extracellular vesicle-mediated transfer of the viral invasive factor LMP1 [66]. Further, Kobayashi et al proved that soluble inhibitors of UCH-L1 are effective in reducing lymph node metastasis of HNSCC; therefore, soluble inhibitors of UCH-L1 offer potential forms of treatment for invasive carcinomas, including EBVpositive malignancies [67].…”

Successful treatment of peritoneal recurrence after gastric cancer surgery with intravenous and intraperitoneal paclitaxel combined with S-1 chemotherapy: a case report

“…During the treatment, it is easy to perform a peritoneal lavage cytological examination through the intraperitoneal access port, and the results are used to determine the effects of IP chemotherapy. Recently, Ohzawa showed that the expression pattern of miRNAs in peritoneal exosomes reflects the tumor burden in the peritoneal cavity and suggested its potential as a useful biomarker in the treatment of PM [19]. Because patients with PM lack measurable lesions that are required to decide the therapy, future studies must discover reliable biomarkers reflecting tumor activity in the peritoneum.…”

Biomarkers Associated with Regorafenib First-Line Treatment Benefits in Metastatic Colorectal Cancer Patients: REFRAME Molecular Study

“…Although these miRNAs have already been associated with invasiveness and malignancy of CRC, they had not been until now linked to locoregional recurrence or peritoneal metastasis, although differential expression of other miRNAs, such as hsa-miR-215-5p, hsa-miR-483-5p, and hsa-miR-31-5p, between liver and peritoneal metastases has already been described in CRC [ 43 ]. In gastric cancer, miR-21-5p, miR-92a-3p, miR-223-3p, and miR-324-3p detected in peritoneal fluid are also associated with peritoneal metastasis [ 44 ]. Deregulation of other miRNAs has also been described in other cancers associated with locoregional recurrence.…”