Yip T T, Ngan R K, Lau W H, Poon Y F, Joab I, Cochet C, Cheng A K
Radiotherapy and Oncology Division, Queen Elizabeth Hospital, Kowloon, Hong Kong.
Cancer. 1994 Nov 1;74(9):2414-24. doi: 10.1002/1097-0142(19941101)74:9<2414::aid-cncr2820740905>3.0.co;2-8.
Epstein-Barr virus BZLF-1 replication activator (ZEBRA) is involved in the switch from viral latency to a productive cycle. Previous immunofluorescent study has shown that patients with nasopharyngeal carcinoma (NPC) have elevated immunoglobulin-G (IgG) antibody titres against recombinant ZEBRA protein (ZEBRA/IgG).
The prognostic role of ZEBRA/IgG was further investigated by enzyme-linked immunosorbent assay (ELISA) in 110 NPC patients under long period of clinical follow-up.
Ninety-seven percent (85 of 88) of the patients with NPC had significantly higher ZEBRA/IgG titres (geometrical mean titre, i.e., GMT = 8397) than normal Chinese individuals (GMT = 233 and P < 0.0001). Based on Kaplan-Meier analysis, the actuarial survival in patients with high ZEBRA/IgG titres (25%) after radiotherapy was significantly lower than that of those with low (76%; P = 0.0008) or intermediate titres (62%; P = 0.0036), although the titres taken before treatment did not bear such a relationship. Subdividing the patients into either individual UICC or Ho's stages, those with late-stage disease (UICC Stage 4 and Ho's Stages 3 and 4) and with high ZEBRA/IgG titres also had poorer prognosis than those with disease of the same stages but who had low titres. Poor prognosis in those with high titres could be associated with a high risk of distant metastasis because consistent titre increase was found in the majority of patients who later developed distant metastasis either in the lung or liver. Only a minimal increase was found in patients with recurrence in the cervical lymph nodes. No consistent increase was observed, however, in patients whose disease was in remission or the majority of those with bone metastasis or local recurrence in the nasopharynx.
The postradiotherapy ZEBRA/IgG titre could be a potentially useful marker for differentiating NPC patients with poor prognosis from those at high risk for the development of distant metastasis to the lung or liver.
爱泼斯坦-巴尔病毒BZLF-1复制激活因子（ZEBRA）参与病毒从潜伏状态向增殖周期的转变。先前的免疫荧光研究表明，鼻咽癌（NPC）患者针对重组ZEBRA蛋白的免疫球蛋白G（IgG）抗体滴度升高（ZEBRA/IgG）。
通过酶联免疫吸附测定（ELISA）对110例接受长期临床随访的NPC患者进一步研究ZEBRA/IgG的预后作用。
97%（88例中的85例）的NPC患者ZEBRA/IgG滴度（几何平均滴度，即GMT = 8397）显著高于正常中国个体（GMT = 233，P < 0.0001）。基于Kaplan-Meier分析，放疗后ZEBRA/IgG滴度高的患者（25%）的精算生存率显著低于滴度低的患者（76%；P = 0.0008）或滴度中等的患者（62%；P = 0.0036），尽管治疗前的滴度不存在这种关系。将患者分为国际抗癌联盟（UICC）或何氏分期的个体，晚期疾病（UICC 4期和何氏3期及4期）且ZEBRA/IgG滴度高的患者的预后也比相同分期但滴度低的患者差。滴度高的患者预后不良可能与远处转移风险高有关，因为在大多数后来发生肺或肝远处转移的患者中发现滴度持续升高。在颈部淋巴结复发的患者中仅发现最小程度的升高。然而，在疾病缓解的患者或大多数有骨转移或鼻咽癌局部复发的患者中未观察到持续升高。
放疗后的ZEBRA/IgG滴度可能是区分预后不良的NPC患者和有发生肺或肝远处转移高风险患者的潜在有用标志物。
