The Role of KRAS GTPase Activation and Epstein-Barr Virus Antibodies in the Molecular Etiology and Immune Dysregulation of Lung Cancer

Abstract

Lung cancer is the largest cause of cancer-related mortality worldwide, constituting 18.4% of all cancer deaths, hence causing considerable economic and societal repercussions. The Epstein-Barr virus (EBV) is the first recognized human oncogenic virus capable of establishing asymptomatic, lifelong persistence. The KRAS gene, a member of the Rat sarcoma oncogene family, accounts for 85% of RAS mutations identified in human cancers and is present in 35% of lung adenocarcinomas (LUADs). This work examines the relationship between EBV IgG seropositivity, KRAS mutation-related immunogenicity, and the genetic polymorphism rs121913238, emphasizing their collective influence on oncogenic signaling, immune evasion, and modifications in the tumor microenvironment. Serum and whole blood samples (n=100) were evaluated via ELISA to measure EBV IgG and KRAS antibody levels, while conventional PCR and Sanger sequencing were utilized for SNP identification in 30 samples. EBV IgG levels were markedly higher in patients than in controls (P=0.0003); conversely, KRAS antibody levels did not exhibit a significant difference between the groups (P=0.187), and no link was detected between KRAS and EBV levels. The rs121913238 polymorphism was absent in the examined samples. Nonetheless, another SNP, rs11836509, was detected in eight samples (six patients and two controls) and was initially linked to lung cancer, necessitating more exploration.