Abstract: Objective EBV associated gastric cancer (EBVaGC), also called EBV positive gastric cancer had been paid much attention due to the possible suitable group for immunotherapy, which was different with EBV non-associated gastric cancer (EBVnGC) in various characteristics. This study aims to explore the molecular differences between them by omics in order to provide a basis for treatment options. Methods Chromogenic in situ hybridization was used to detect EBV-RNA status of surgical specimens and PDXs from patients. Targeted capture sequencing and protein mass spectrometry were implented to analyze the different molecules, further verify the PD-L1 expression by immunochemistry in EBV positive and negative tissues. Results Compared with EBVnGC, the higher PIK3CA mutation rate and lower TP53 mutation rate were detected in EBVaGC. Post-transcriptional regulation molecules were up-regulated and molecules associated with metabolism and oxidative phosphorylation were down-regulated in EBVaGC. PD-L1 expression in EBV positive PDXs was significantly higher than that in EBV negative (76.92% vs 25.0%, P<0.05). Conclusions There is a great difference between EBVaGC and EBVnGC on genetic variation and expression, which provides the basis for further exploration of the molecular mechanism and treatment strategy of EBVaGC.

Key words: EBVaGC, Molecular characteristics, PD-L1, Immunotherapy