About 10% of gastric carcinomas (GC) harbor monoclonal Epstein-Barr virus (EBV). Anti-EBV antibody profiles distinguished patients with EBV-associated GC (EBVaGC) from those with EBV-negative GC (EBVnGC) in a previous study. Therefore, we examined these markers in a larger cohort with patient samples from Japan, a high gastric cancer-risk population.

Multi-microbial Nucleic Acid Programmable Protein Array was used to test stored sera from 102 EBVaGC and 131 EBVnGC patients.

Among 89 IgG antibodies against EBV-specific antigens, 32 (36%) showed at least 10% seroprevalence in either EBVaGC or EBVnGC patients. Seropositivity of ten anti-EBV antibodies (LF2, BDLF2, BXLF1, BRLF1, BKRF3, BHRF1, BORF2, BZLF1, BNRF1, and BALF2) were significantly higher in EBVaGC patients than those with EBVnGC, with a maximal odds ratio of 22 (95% confidence interval: 5.2, 195) for anti-LF2. The ten antibodies collectively had an area under the receiver operating curve of 0.747 (95% CI: 0.683, 0.811). Five of these markers (LF2, BRLF1, BXLF1, BORF2, and BALF2) were among the seven discriminatory antibodies identified in the previous study. These differences in serological reactions were seen for proteins in the lytic infection phase, but not for those in the latent infection phase, consistent with the previous results.

The present study confirms the utility of anti-EBV serology for non-invasive detection of EBVaGC.