Development of Epstein-Barr virus-associated gastric cancer: Infection, inflammation, and oncogenesis

Abstract

Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) cells originate from a single-cell clone infected with EBV. However, more than 95% of patients with gastric cancer have a history of Helicobacter pylori ( H. pylori ) infection, and H. pylori is a major causative agent of gastric cancer. Therefore, it has long been argued that H. pylori infection may affect the development of EBVaGC, a subtype of gastric cancer. Atrophic gastrointestinal inflammation, a symptom of H. pylori infection, is observed in the gastric mucosa of EBVaGC. Therefore, it remains unclear whether H. pylori infection is a cofactor for gastric carcinogenesis caused by EBV infection or whether H. pylori and EBV infections act independently on gastric cancer formation. It has been reported that EBV infection assists in the onco-genesis of gastric cancer caused by H. pylori infection. In contrast, several studies have reported that H. pylori infection accelerates tumorigenesis initiated by EBV infection. By reviewing both clinical epidemiological and experimental data, we reorganized the role of H. pylori and EBV infections in gastric cancer formation.

Immunotherapy of gastric cancer: Present status and future perspectives

“…Therefore, it remains unclear whether H. pylori infection is a cofactor for EBV-induced gastric carcinogenesis or whether H. pylori and EBV act independently in the development of GC. The possibilities are either that EBV infection participates in H. pylori -induced GC tumorigenesis, or that H. pylori infection accelerates EBV-initiated carcinogenesis[ 29 ].…”

The role of EBV-encoded miRNA in EBV-associated gastric cancer

“…EBVaGC is identified as EBV-infected tumor cells by polymerase chain reaction analysis and in situ hybridization and characterized by lymphoepithelioma-like histology, unique clinical features, and relatively desirable prognosis compared to non-EBV-associated cases (EBVnGC) ( 11 ). EBVaGC is associated with Caucasian or Hispanic ethnicity, male gender, younger age, history of gastric surgery, and unhealthy lifestyles (such as smoking and consumption of salty foods) ( 12 – 15 ). Helicobacter pylori infection has long been considered a causative factor for GC.…”

Tremella fuciformis polysaccharides induce ferroptosis in Epstein–Barr virus-associated gastric cancer by inactivating NRF2/HO-1 signaling

“…Studies have found that EBV-associated gastric cancer (EBVaGC) accounts for approximately 10% of gastric cancers worldwide and that EBV infection is positively associated with the risk of gastric cancer [ 4 , 5 ]. More than 95% of patients with gastric cancer are found to have a typical history of Helicobacter pylori ( H. pylori ) infection, and EBV infection can promote the development of gastric cancer caused by H. pylori infection [ 6 ]. A recent study found that when normal gastric epithelial cells are infected with EBV, the intracellular microenvironment undergoes significant changes thereby promoting GC [ 7 ].…”

“…Morphologically, cells undergoing ferroptosis have intact cytosolic membranes, normal-sized nuclei, no chromatin condensation, dense mitochondria, and residual cristae. Biochemically, cells undergoing ferroptosis exhibit elevated Fe 2+ levels, increased ROS levels, inactivation or depletion of glutathione peroxidase 4 (GPX4), inhibition of cystine/glutamate transporter protein SLC7A11 (also xCT, system xc-), and accumulation of lipid metabolites [ 6 ]. The transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) is a key member of endogenous antioxidant defense systems [ 13 , 14 ].…”