Deciphering the Differences Between Epstein-Barr Virus-Associated and Negative Gastric Cancer in the Prospect of CDKN2A Genomic Alterations and Lymphoid Infiltration

Abstract

Background: Gastric cancer (GC) is a major health concern worldwide. One important contributing factor is the presence of the Epstein-Barr virus (EBV). However, the molecular pattern of how EBV participates in the malignant transition process remains unclear.

Methods: GC samples were stained by immunohistochemistry, fluorescent and EBV-encoded small RNA in situ hybridization to identify CD8 expression, CDKN2A genomic alteration, and EBV existence. Functional potentials of EBV infection were predicted by bioinformatic enrichment analysis.

Results: CDKN2A genestayed intact in all EBV-associated GC cases. Meanwhile, CDKN2A deletion (8.43% cases) was exclusive to EBV-negative GC cases. Furthermore, EBV infection was positively correlated with CD8+T cell infiltration, and both of them predicted better prognosis.

Conclusion: This study highlighted the comprehensive impact of EBV infection in GC formation and proposed a thought-provoking observation for further investigation into the roles of CDKN2A and EBV infection in gastric tumorigenesis.

Keywords: CD8+ T cell infiltration; CDKN2A; Epstein–Barr virus; gastric cancer.