Identification of anti-Epstein-Barr virus (EBV) antibody signature in EBV-associated gastric carcinoma.

Identification of anti-Epstein-Barr virus (EBV) antibody signature in EBV-associated gastric carcinoma.
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DOI:
10.1007/s10120-021-01170-z
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发表时间:
2021-07
期刊:
Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association
影响因子:
--
通讯作者:
Rabkin CS
Rabkin CS
中科院分区:
其他
文献类型:
--
作者:
Song L;Song M;Camargo MC;Van Duine J;Williams S;Chung Y;Kim KM;Lissowska J;Sivins A;Gao W;Karthikeyan K;Park J;Leja M;Cohen JI;LaBaer J;Qiu J;Rabkin CS

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大约10%的胃癌(GC)含有EB病毒(EBV)DNA。我们的特点是GC特异性抗体反应,这种常见的感染,这可能提供一个非侵入性的方法来检测EBV阳性GC和阐明其致癌作用。来自EBV阳性(n=28)和EBV阴性(n=34)拉脱维亚GC患者的血浆样品在多微生物核酸可编程蛋白阵列(EBV-NAPPA)上针对85种EBV蛋白进行免疫分析。将每份样本的抗体应答标准化为与所有抗原的中位信号强度(MNI)的比值,血清阳性定义为MNI ≥2。通过酶联免疫吸附试验(ELISA)验证对肿瘤EBV状态具有≥20%灵敏度和95%特异性的抗体,并在来自韩国和波兰的独立样本中进行验证(n=24例EBV阳性,n=65例EBV阴性)。EBV-NAPPA法在≥10%的EBV阳性或阴性胃癌患者中检出40例抗EBV IgG和8例伊加抗体,其中9例IgG抗体可鉴别肿瘤EBV状态。通过ELISA验证了这9个中的8个,并验证了7个:抗LF 2(比值比=110.0)、抗BORF 2(54.2)、抗BALF 2(44.1)、抗BaRF 1(26.7)、抗BXLF 1(12.8)、抗BRLF 1(8.3)和抗BLLF 3(5.4)。前三个具有用于区分肿瘤EBV状态的0.81-0.85的受试者操作特征曲线下面积。EBV相关的GC特异性体液反应专门针对溶解周期立即早期和早期抗原,不像其他EBV相关的恶性肿瘤,如鼻咽癌和淋巴瘤,其中体液反应主要针对晚期溶解抗原。特异性抗EBV抗体可用于EBV阳性胃癌的临床诊断、流行病学研究和基于免疫的精确治疗。
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. 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). Forty anti-EBV IgG and 8 IgA antibodies were detected by EBV-NAPPA in ≥10% of EBV-positive or EBV-negative GC patients, of which 9 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. 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.
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DOI: 10.1007/978-1-61779-043-0_15
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期刊: PROTEIN MICROARRAY FOR DISEASE ANALYSIS: METHODS AND PROTOCOLS
影响因子: --
作者:
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