Comprehensive analysis of differential expression and functions of DPYSL3 in EBV-positive and -negative gastric cancer

Compared with Epstein – Barr virus (EBV)-negative gastric cancer (EBVnGC), EBV-associated GC (EBVaGC) has distinct clinicopathological features. This study aimed to provide a laboratory basis for the early diagnosis and precise treatment of GC. The differential expression of Dihydropyrimidinase-like 3 (DPYSL3) in EBVaGC and EBVnGC cells was identified by quantitative proteomic, Gene Expression Omnibus (GEO) database, R software, and western blot. Transwell, Cell Counting Kit-8, colony formation, and flow cytometry experiments were conducted to detect cellular biological functions. High DPYSL3 expression was associated with poor prognosis of GC and closely related to migration and epithelial – mesenchymal transition (EMT) of GC cells and tumor infiltration of immune cells. DPYSL3 downregulation inhibited the migration and EMT process of GC cells without a significant effect on their proliferation or apoptosis. The results further confirmed that EBV could inhibit DPYSL3 expression by activating the AMPK signaling pathway through the encoded latent membrane protein 2A (LMP2A). The results indicate that DPYSL3 can promote the migration of GC cells and tumor-infiltrating immune cells, whereas the EBV-encoded LMP2A inhibits DPYSL3 expression by activating the AMPK signaling pathway. Differences in DPYSL3 expression between EBVaGC and EBVnGC may provide new strategies for personalized treatment of GC. Epstein – Barr virus (EBV)-associated gastric cancer is a distinct subtype of gastric cancer, and EBV infection plays a key role in causing it. EBV can use a substance called latent membrane protein 2A to trigger a “signaling pathway” in the cancer cells. This trigger then reduces the amount of protein called DPYSL3 in the cells. When there is a lot of DPYSL3, people with gastric cancer tend to have worse outcomes (like harder recovery or higher chance of the cancer coming back). What’s more, too much DPYSL3 helps gastric cancer cells spread, change their form to move more easily, and draw in certain immune cells that actually help the cancer grow and spread.