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- Title
Identification of anti-Epstein-Barr virus (EBV) antibody signature in EBV-associated gastric carcinoma.
- Authors
Song, Lusheng; Song, Minkyo; Camargo, M. Constanza; Van Duine, Jennifer; Williams, Stacy; Chung, Yunro; Kim, Kyoung-Mee; Lissowska, Jolanta; Sivins, Armands; Gao, Weimin; Karthikeyan, Kailash; Park, Jin; Leja, Marcis; Cohen, Jeffrey I.; LaBaer, Joshua; Qiu, Ji; Rabkin, Charles S.
- Abstract
Background: Around 10% of gastric carcinomas (GC) contain Epstein–Barr virus (EBV) DNA. We characterized the GC-specific antibody response to this common infection, which may provide a noninvasive method to detect EBV-positive GC and elucidate its contribution to carcinogenesis. Methods: Plasma samples from EBV-positive (n = 28) and EBV-negative (n = 34) Latvian GC patients were immune-profiled against 85 EBV proteins on a multi-microbial Nucleic Acid Programmable Protein Array (EBV-NAPPA). Antibody responses were normalized for each sample as ratios to the median signal intensity (MNI) across all antigens, with seropositivity defined as MNI ≥ 2. Antibodies with ≥ 20% sensitivity at 95% specificity for tumor EBV status were verified by enzyme-linked immunosorbent assay (ELISA) and validated in independent samples from Korea and Poland (n = 24 EBV-positive, n = 65 EBV-negative). Results: Forty anti-EBV IgG and eight IgA antibodies were detected by EBV-NAPPA in ≥ 10% of EBV-positive or EBV-negative GC patients, of which nine IgG antibodies were discriminative for tumor EBV status. Eight of these nine were verified and seven were validated by ELISA: anti-LF2 (odds ratio = 110.0), anti-BORF2 (54.2), anti-BALF2 (44.1), anti-BaRF1 (26.7), anti-BXLF1 (12.8), anti-BRLF1 (8.3), and anti-BLLF3 (5.4). The top three had areas under receiver operating characteristics curves of 0.81–0.85 for distinguishing tumor EBV status. Conclusions: The EBV-associated GC-specific humoral response was exclusively directed against lytic cycle immediate-early and early antigens, unlike other EBV-associated malignancies such as nasopharyngeal carcinoma and lymphoma where humoral response is primarily directed against late lytic antigens. Specific anti-EBV antibodies could have utility for clinical diagnosis, epidemiologic studies, and immune-based precision treatment of EBV-positive GC.
- Subjects
POLAND; SOUTH Korea; STOMACH cancer; VIRUS identification; RECEIVER operating characteristic curves; ANTIBODY formation; IMMUNOGLOBULIN G
- Publication
Gastric Cancer, 2021, Vol 24, Issue 4, p858
- ISSN
1436-3291
- Publication type
Article
- DOI
10.1007/s10120-021-01170-z