Abstract 5185: Identification of a new candidate therapeutic target for gastric cancer by in silico analysis

2018 
Gastric Cancer (GC) is a leading cause of global cancer mortality, with high incidence rates in Asia including Japan. Although recent studies have provided valuable insights into identification of major driver genes, there are still little therapeutic targets and prognostic markers of GC. Here, we report that a novel driver gene, OverExpressed in Gastric Cancer 1 (OEGC1), would induce cell proliferation and migration of GC.Analyzing gene expression profiles by RNA-Seq and relevant clinical data in TCGA dataset, we identified candidate genes whose mRNA expression was higher in tumor tissues than in non-tumorous and associated with poor prognosis. Through further expression analysis and Cox proportional hazards regression analysis of those candidates, we identified OEGC1 as the most prominent candidate for driver gene. OEGC1 mRNA was expressed highly especially in intestinal type GC. The prognosis of the OEGC1 high-expressed intestinal type GC patients was as poor as that of diffuse type GC patients. Immunohistochemical analysis showed that overexpression of OEGC1 was ectopically found in the tumor cell junctions located in the infiltrated region of tumor. By silencing endogenous OEGC1 using siRNAs, cell proliferation was significantly suppressed and G0/G1 arrest was induced in NUGC3, AGS and MKN7 cells with relatively higher OEGC1 expression. Transwell assay showed that the number of migrated cells was significantly lower for siRNA-OEGC1-transfected cells than for control cells. Our findings suggested that aberrant expression of OEGC1 might play an important role in tumorigenesis of GC, and that OEGC1 might be a possible therapeutic target in GC. Citation Format: Tomohiro Kohmoto, Kiyoshi Masuda, Katsutoshi Shoda, Yuji Fujita, Shoichiro Tange, Daisuke Ichikawa, Eigo Otsuji, Issei Imoto. Identification of a new candidate therapeutic target for gastric cancer by in silico analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5185.
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