Discovery and Validation of Biomarkers for Epstein-Barr Virus Associated Gastric Cancer

• A functional EBV proteome microarray covering 72 viral proteins was developed and applied to profile antibody responses in gastric cancer patients, revealing an IgG-skewed humoral signature specific to EBVaGC. • A five-analyte panel (LF2_IgG, BBLF2_IgG, BLRF2_IgG, BPLF1-2_IgA, and BGLF4_IgA) was identified and validated, achieving an AUC of 0.93 in an independent validation set (n=316). • In a community-based screening cohort (n=474), the panel achieved 87.3% sensitivity and 88.3% specificity for distinguishing EBVaGC from non-malignant gastric conditions, with an AUC of 0.94. • The study establishes a serological framework for EBVaGC diagnosis, offering a scalable strategy for population-level screening that could improve clinical management of this virus-driven malignancy.