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系统分析结肠癌中的人类致癌病毒,揭示了 EBV 在淋巴浸润中的潜伏。

Systematic analysis of human oncogenic viruses in colon cancer revealed EBV latency in lymphoid infiltrates.

机构信息

Department of Diagnostic Medicine, Molecular Virology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

Department of Onco-Hematology, Oncology Section, Fondazione IRCCS Policlinico San Matteo, V.le Camillo Golgi 19, 27100 Pavia, Italy.

出版信息

Infect Agent Cancer. 2014 Jun 3;9:18. doi: 10.1186/1750-9378-9-18. eCollection 2014.

Abstract

BACKGROUND

Environmental factors may play a role in colon cancer. In this view, several studies investigated tumor samples for the presence of various viral DNA with conflicting results.

FINDINGS

We undertook a systematic DNA analysis of 44 consecutive, prospectively collected primary tumor samples by real time and qualitative PCR for viruses of known or potential oncogenic role in humans, including polyomavirus (JCV, BKV, Merkel cell polyomavirus), HPV, HTLV, HHV-8 and EBV. Negative controls consisted of surgical resection margins. No evidence of genomic DNA fragments from tested virus were detected, except for EBV, which was found in a significant portion of tumors (23/44, 52%). Real-time PCR showed that EBV DNA was present at a highly variable content (median 258 copies in 10(5) cells, range 15-4837). Presence of EBV DNA had a trend to be associated with high lymphocyte infiltration (p = 0.06, χ2 test), and in situ hybridization with EBER1-2 probes revealed latency in a fraction of these lymphoid cells, with just a few scattered plasma cells positive for BZLF-1, an immediate early protein expressed during lytic replication. LMP-1 expression was undetectable by immunohistochemistry.

CONCLUSIONS

These results argue against a significant involvement of the tested oncogenic viruses in established colon cancer.

摘要

背景

环境因素可能在结肠癌中发挥作用。从这一观点出发,有几项研究针对各种已知或潜在致癌作用的病毒 DNA 在肿瘤样本中的存在情况进行了调查,但结果相互矛盾。

发现

我们通过实时和定性聚合酶链反应对 44 例连续前瞻性采集的原发性肿瘤样本进行了系统的 DNA 分析,用于检测已知或潜在致癌作用的人类病毒,包括多瘤病毒(JCV、BKV、Merkel 细胞多瘤病毒)、HPV、HTLV、HHV-8 和 EBV。阴性对照由手术切除边缘组成。除 EBV 外,未检测到测试病毒的基因组 DNA 片段,而 EBV 在很大一部分肿瘤中存在(23/44,52%)。实时 PCR 显示 EBV DNA 存在高度可变的含量(中位数为 10(5) 个细胞中的 258 个拷贝,范围为 15-4837)。EBV DNA 的存在有趋势与高淋巴细胞浸润相关(p=0.06,卡方检验),EBER1-2 探针的原位杂交显示这些淋巴细胞中有一部分处于潜伏状态,只有少数浆细胞呈 BZLF-1 阳性,BZLF-1 是裂解复制期间表达的一种早期蛋白。免疫组化未检测到 LMP-1 表达。

结论

这些结果表明,所测试的致癌病毒在已建立的结肠癌中没有明显的参与。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b75a/4058445/525063def312/1750-9378-9-18-1.jpg

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