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胃腺癌中 JC 病毒的存在与患者的年龄、肠组织学类型和肿瘤抑制基因的异常甲基化相关。

The presence of JC virus in gastric carcinomas correlates with patient's age, intestinal histological type and aberrant methylation of tumor suppressor genes.

机构信息

Department of Pathology, Farhat-Hached Hospital of Sousse, Sousse, Tunisia.

出版信息

Mod Pathol. 2010 Apr;23(4):522-30. doi: 10.1038/modpathol.2009.184. Epub 2010 Jan 15.

Abstract

JC virus (JCV) is a neurotropic polyomavirus and the causative agent of progressive multifocal leukoencephalopathy. A role for JCV in gastrointestinal malignancies has been recently suggested. This study was carried out to determine the prevalence of polyomaviruses including JCV, BKV and SV40 in gastric cancers in Tunisia and to determine the clinicopathological characteristics of virus-associated gastric carcinomas. The presence of polyomaviruses DNA sequences was surveyed in 61 cases of primary gastric carcinomas and in 53 paired non-tumor gastric mucosa by PCR. Findings were correlated to clinicopathological parameters, p53 expression and methylation status of 11 tumor-related genes. Using PCR assays, JCV T-antigen sequence was more frequently detected in gastric carcinomas than in non-tumor gastric mucosa (26 vs 6%, P=0.03), while those of SV40 and BKV were not detected in any cases. Correlation analysis showed that JCV had higher frequency in patients older than 55 years (P=0.034) and in the intestinal histological type (P=0.04). With regard to methylation status, P16 and P14 showed significantly higher methylation frequencies in JCV-positive gastric carcinomas than in JCV-negative cases (P=0.007 and P=0.003, respectively). Moreover, the mean of the methylation index was significantly higher in JCV-positive than in JCV-negative cases (P=0.024). In multivariate logistic regression analysis, age of patients and the methylation index are only the two independent factors associated with JCV infection. Kaplan-Meier survival analysis showed a trend toward better survival for JCV-associated gastric carcinomas patients (log-rank, P=0.11). Our study suggests a role of JCV as cofactor in the pathogenesis of the intestinal type of gastric carcinomas in older persons.

摘要

JC 病毒(JCV)是一种神经嗜性多瘤病毒,也是进行性多灶性白质脑病的病原体。最近有研究表明 JCV 与胃肠道恶性肿瘤有关。本研究旨在确定聚瘤病毒(包括 JCV、BKV 和 SV40)在突尼斯胃癌中的流行情况,并确定病毒相关胃癌的临床病理特征。采用 PCR 法检测 61 例原发性胃癌和 53 对配对非肿瘤胃黏膜中多瘤病毒 DNA 序列。将检测结果与临床病理参数、p53 表达和 11 个肿瘤相关基因的甲基化状态进行相关性分析。使用 PCR 检测,JCV T 抗原序列在胃癌中的检出率高于非肿瘤胃黏膜(26%比 6%,P=0.03),而 SV40 和 BKV 均未检出。相关性分析显示,JCV 在年龄大于 55 岁的患者(P=0.034)和肠型组织学类型的患者(P=0.04)中更为常见。关于甲基化状态,P16 和 P14 在 JCV 阳性胃癌中的甲基化频率明显高于 JCV 阴性病例(P=0.007 和 P=0.003)。此外,JCV 阳性病例的甲基化指数平均值明显高于 JCV 阴性病例(P=0.024)。在多变量逻辑回归分析中,患者年龄和甲基化指数是与 JCV 感染相关的两个独立因素。Kaplan-Meier 生存分析显示,JCV 相关胃癌患者的生存时间有延长趋势(log-rank,P=0.11)。本研究提示 JCV 可能作为老年人肠型胃癌发病的协同因素。

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