Circulating Antibodies against Epstein–Barr Virus (EBV) and p53 in EBV-Positive and -Negative Gastric Cancer
Year: 2019
Type: review
Study design: Observational Study
Abstract: Background: Epstein–Barr virus (EBV)-positive gastric cancers have clinicopathologic differences from EBV-negative tumors and lack TP53 mutation. Serologic profiles may inform viral contribution to carcinogenesis. Methods: We compared humoral responses of EBV-positive (n = 67) and EBV-negative (n = 137) patients with gastric cancer from the International EBV-Gastric Cancer Consortium. Serum antibodies against four EBV proteins, nuclear (EBNA), viral capsid (VCA), early-diffuse (EA-D), and Zta replication activator (ZEBRA), and to p53 were assessed by multiplex assays. OR of antibody level tertiles (T1–T3) were adjusted by logistic regression. We also conducted a meta-analysis of reported anti-p53 seropositivity in gastric cancer. Results: Consistent with EBV's ubiquity, 99% of patients were seropositive for anti-EBNA and 98% for anti-VCA, without difference by tumor EBV status. Seropositivity varied between patients with EBV-positive and EBV-negative tumors for anti-EA-D (97% vs. 67%, respectively, P < 0.001) and anti-ZEBRA (97% vs. 85%, respectively, P = 0.009). Adjusted ORs (vs. T1) for patients with EBV-positive versus EBV-negative tumors were significantly elevated for higher antibodies against EBNA (2.6 for T2 and 13 for T3), VCA (1.8 for T2 and 2.4 for T3), EA-D (6.0 for T2 and 44 for T3), and ZEBRA (4.6 for T2 and 12 for T3). Antibodies to p53 were inversely associated with EBV positivity (3% vs. 15%; adjusted OR = 0.16, P = 0.021). Anti-p53 prevalence from the literature was 15%. Conclusions: These serologic patterns suggest viral reactivation in EBV-positive cancers and identify variation of p53 seropositivity by subtype. Impact: Anti-EBV and anti-p53 antibodies are differentially associated with tumor EBV positivity. Serology may identify EBV-positive gastric cancer for targeted therapies.
Authors: M. Constanza Camargo, Kyoung-Mee Kim, Keitaro Matsuo, Javier Torres, Linda M. Liao, Douglas Morgan, Angelika Michel, Tim Waterboer, Minkyo Song, Margaret L. Gulley, Ricardo L. Dominguez, Yasushi Yatabe, Sung Kim, Gustavo Cortes-Martinez, Jolanta Lissowska, Jovanny Zabaleta, Michael Pawlita, Charles S. Rabkin
Institutions: National Cancer Institute, Division of Cancer Epidemiology and Genetics, Samsung Medical Center, Sungkyunkwan University, Aichi Cancer Center, Mexican Social Security Institute, Vanderbilt University, University of Alabama at Birmingham, UAB Medicine, German Cancer Research Center, University of North Carolina at Chapel Hill, UNC Lineberger Comprehensive Cancer Center, Aichi Cancer Center Hospital, The Maria Sklodowska-Curie National Research Institute of Oncology, Louisiana State University Health Sciences Center New Orleans
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: KRAS mutations in lung cancer, Mentoring Translational Researchers in Louisiana, Etiological Studies of Gastric Carcinoma, Targeted chemoprevention of gastric carcinogenesis in high risk populations, Platform of Supporting Cohort Study and Biospecimen Analysis, Gastric Cancer Epidemiology Initiative in Central America, Cancer Center Support Grant, Louisiana Clinical and Translational Science Center
OpenAlex ID: W2989439738