A nine-gene signature as prognostic biomarker in gastric cancer by bioinformatics analysis.

Purpose: The prognosis of advanced gastric cancer (GC) remains poor. It is urgent and necessary to find suitable prognostic markers. miR-619-5p is highly expressed in GC. However, the value of miR-619-5p and its target genes as prognostic biomarkers of GC is unclear.

Methods: RT-PCR was performed to verify the expression of miR-619-5p in GC cell lines and their exosomes. Western blotting and transmission electron microscope were used to identify exosomes. The target genes of miR-619-5p were predicted by RNA22 and TargetScan. The differentially expressed genes (DEGs) and prognosis-related genes (PRGs) were obtained using The Cancer Genome Atlas (TCGA) database. The DAVID database was used to analyse pathway enrichment and functional annotation of common target genes. The STRING database and Cytoscape software were used to screen key genes and visualize their functional modules. The survival analysis was conducted using TCGA and Kaplan-Meier Plotter (KMP) databases. Finally, a prognostic model was constructed on the foundation of the key genes to assess the reliability of the screening process.

Results: The expression of miR-619-5p in GC cells and their exosomes was proved to be significantly higher than that in normal cell lines. There are 129 common target genes involved in 3 pathways and 28 functional annotations. Finally, nine key target genes of GC (BRCA1, RAD51, KIF11, ERCC6L, BRIP1, TIMELESS, CDC25A, CLSPN and NCAPG2) were identified, and a prognostic model was successfully constructed with a good predictive ability.

Conclusions: The model of 9-gene signature could effectively predict the prognosis of GC, and have great potential to be novel prognostic factors and therapeutic targets for patients with GC.