Identification of differentially expressed miRNAs derived from serum exosomes associated with gastric cancer by...

To explore the differentially expressed microRNAs (DEMs) in serum exosomes between gastric cancer (GC) patients and healthy people to provide new targets for GC diagnosis and treatment.

DEMs in serum exosomes were screened by microarray analysis and verified by RT-qPCR. The target genes of DEMs were predicted using Targetscan and miRTarBase databases and then overlapped with the DEGs of STAD in TCGA database to obtain the common target genes. Biological function and pathway enrichment were analyzed using enrichr database, and a PPI network was constructed using STRING database. The potential target genes of DEMs were identified using the MCODE and cytoHubba plug-ins of Cytoscape software. Survival analysis were conducted using KMP and TCGA databases. The DEMs -target genes-pathways network was established using Cytoscape software. A Cox proportional hazards regression model formed by optimal target genes was used to access the reliability of this prediction process.

Three serum exosomal microRNAs (exo-miRNAs, has-miR-1273 g-3p, has-miR-4793-3p, has-miR-619-5p) were identified to be highly expressed in GC patients and performed excellent diagnostic ability. A total of 179 common target genes related to GC were predicted. They were mainly involved in 79 GO functional annotations and 6 KEGG pathways. The prognostic model formed by eight optimal target genes (TIMELESS, DNA2, MELK, CHAF1B, DBF4, PAICS, CHEK1 and NCAPG2), which were low-risk genes of GC, also performed perfect prognostic ability.

Serum exosomal has-miR-1273 g-3p, has-miR-4793-3p and has-miR-619-5p can be used as new diagnostic biomarkers for GC. Among them, serum exosomal hsa-miR-1273 g-3p / hsa-miR-4793-3p targets MELK and hsa-miR-619-5p targets NCAPG2 were identified as novel mechanisms involved in the development of GC. It provides new targets for the diagnosis and treatment of GC by exo-miRNAs.