Analysis of epstein‐barr virus infection in nasopharyngeal biopsies from a group at high risk of nasopharyngeal carcinoma

Ck, Sam; La, Brooks; Niedobitek, Gerald; Lw, Young; Prasad, U.; Rickinson, A. B.

doi:10.1002/ijc.2910530616

Cited by 97 publications

(38 citation statements)

References 20 publications

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“…48 Early recognition of disease onset remains an important factor in survival, as the majority of cases are at an advanced stage upon diagnosis. One of the hallmarks of NPC is the association with EBV (12,13). While the mechanism by which EBV contributes to the initiation or progression of NPC is still not understood, numerous studies have focused on using EBV as a biomarker for recognition, and even therapy, of NPC.…”

Section: Discussionmentioning

confidence: 99%

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Circulating Epstein–Barr virus microRNAs miR‐BART7 and miR‐BART13 as biomarkers for nasopharyngeal carcinoma diagnosis and treatment

Zhang

Zong

Shen

et al. 2014

Intl Journal of Cancer

104

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More than 75% of nasopharyngeal carcinoma (NPC) patients have already developed local or regional spread at diagnosis, which hampers effective treatment and results in a poor prognosis. It is essential to characterize more sensitive and specific biomarkers for screening of high risk individuals and assessment of NPC treatment effectiveness. NPC is an Epstein-Barr virus (EBV) associated tumor in which only a few viral proteins but more than 20 BamHI A rightward transcripts (BART) microRNAs are detected, at abundant levels. We hypothesized that these BART microRNAs may be novel biomarkers for NPC. Systematic analysis of EBV BART microRNA expression profiles in EBV latently infected Mutu I and Mutu III cell lines, EBV-harboring NPC and noncancerous NP cells found that miR-BART3, miR-BART7 and miR-BART13 microRNAs are highly expressed and regularly secreted into the extracellular environment of NPC cells. These BART microRNAs were evaluated for used as potential NPC biomarkers. Analysis of plasma specimens obtained from NPC patients (n 5 89), and healthy (n 5 28) and non-NPC tumor patient controls (n 5 18) found levels of both miR-BART7 and miR-BART13, but not miR-BART3, to be distinctly presence among NPC patients, with elevated levels being particularly apparent among patients with advanced disease. Receiver operating characteristic curve analysis combining miR-BART7 and miR-BART13 levels produces a 90% predictive value for the presence of NPC. Analysis of 41 NPC patients before and after radiotherapy showed that miR-BART7 and miR-BART13, but not miR-BART3, were diminished after treatment. These results indicate that EBV microRNAs, miR-BART7 and miR-BART13, may constitute useful new serological biomarkers for diagnosis of NPC and prediction of treatment efficacy.

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Section: Discussionmentioning

confidence: 99%

“…11,12 It is notable that EBV is rarely detected in noncancerous epithelial cells, even in the areas adjacent to NPC. 13 EBV is thus an excellent biomarker for NPC diagnosis. In situ detection of the EBV noncoding transcripts EBER1 and EBER2 in biopsies has been routinely used in clinical diagnosis of NPC.…”

mentioning

confidence: 99%

Circulating Epstein–Barr virus microRNAs miR‐BART7 and miR‐BART13 as biomarkers for nasopharyngeal carcinoma diagnosis and treatment

Zhang

Zong

Shen

et al. 2014

Intl Journal of Cancer

104

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“…Nevertheless, EBV has not been detected in normal epithelial cells or those adjacent to NPC, and the only examples of latent infection are those of carcinomas associated. 16,17 This fact indicates that EBV is able to stably exist in epithelial tumor cells in vivo, and the occurrence of a latent infection is a substantial contributing factor to the development of carcinoma. Such situations prompt us to exploit a malignant model for investigating EBV infection and activity in epithelial cells.…”

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confidence: 99%

Epstein–Barr virus facilitates the malignant potential of immortalized epithelial cells: from latent genome to viral production and maintenance

Tang

et al. 2010

Laboratory Investigation

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Epstein-Barr virus (EBV) is closely associated with several malignancies, including nasopharyngeal carcinoma. To investigate the EBV activity in tumor development, we tried to establish a malignant model of EBV-infected cells in nude mice. On the basis of the Maxi-EBV system, a human embryonic kidney epithelial cell line (293) with a low malignant potential was used for a stable EBV genome infection. The derived cell line, termed 293-EBV, exhibited obvious morphological transformation and significantly increased growth ability, with the cell cycle redistributed. The clonability and tumorigenicity were also substantially accelerated. In 293-EBV cells, the expression level of the transcription factor NF-kB and JNK2 were upregulated. The result suggested that latent membrane protein 1 (LMP1) was an important viral protein responsible for the enhanced malignant potential. Matured and budding virus particles were observed in tumor tissues, confirming the spontaneous reactivation of EBV from latent genome to lytic cycle at the site of tumor development. Primary culture of tumor tissues showed two patterns about the EBV maintenance or not in newly grown cells, and this was dependent on the thickness of the planted tissues. Moreover, the tumor cells lost EBV genome easily when subcultured at low density. Our findings revealed the cell-to-cell contact mechanism, which was required for the EBV maintenance in the tumor cells during the expansion of EBV-infected cells. This mechanism might give an explanation to the phenomenon that EBV genome in epithelial tumor cells becomes easily lost during subculture in vitro. Our results provided further evidence of a function for EBV in the etiology of tumor development.

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“…To date, it is recognized that the virus was present in virtually all the WHO-2 and WHO-3 NPC cells (Sam et al 1993). For WHO-1 keratinizing NPC, the causal role of EBV remains unresolved as the virus could only be found in a few numbers of patients.…”

Section: The Use Of Molecular Markers In Npc Diagnosismentioning

confidence: 99%

Biomarkers in Nasopharyngeal Carcinoma and Ionizing Radiation

Wong¹,

Gao²,

Chan³

2014

Biomarkers in Cancer

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Analysis of epstein‐barr virus infection in nasopharyngeal biopsies from a group at high risk of nasopharyngeal carcinoma

Cited by 97 publications

References 20 publications

Circulating Epstein–Barr virus microRNAs miR‐BART7 and miR‐BART13 as biomarkers for nasopharyngeal carcinoma diagnosis and treatment

Circulating Epstein–Barr virus microRNAs miR‐BART7 and miR‐BART13 as biomarkers for nasopharyngeal carcinoma diagnosis and treatment

Epstein–Barr virus facilitates the malignant potential of immortalized epithelial cells: from latent genome to viral production and maintenance

Biomarkers in Nasopharyngeal Carcinoma and Ionizing Radiation

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