Estrogen induces the expression of <scp>EBV</scp> lytic protein <scp>ZEBRA</scp>, a marker of poor prognosis in nasopharyngeal carcinoma

Dochi, Hirotomo; Kondo, Satoru; Murata, Takayuki; Fukuyo, Masaki; Nanbo, Asuka; Wakae, Kousho; Jiang, Wenping; Hamabe‐Horiike, Toshihide; Tanaka, Mariko; Nishiuchi, Takumi; Mizokami, Harue; Moriyama‐Kita, Makiko; Kobayashi, Eiji; Hirai, Nobuyuki; Komori, Takeshi; Ueno, Takayoshi; Nakanishi, Yosuke; Hatano, Miyako; Endo, Kazuhira; Sugimoto, Hisashi; Wakisaka, Naohiro; Juang, Shin‐Hun; Muramatsu, Masamichi; Kaneda, Atsushi; Yoshizaki, Tomokazu

doi:10.1111/cas.15440

Cited by 13 publications

(12 citation statements)

References 50 publications

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“…CRIP1, on the other hand, is strongly downregulated and has been identified as a biomarker of EBV-associated nasopharyngeal carcinoma 47 . The estrogen receptor-1 protein ESR1 (upregulated), is known to induce the expression of the immediate early viral gene BZLF1 and has been also associated to poor prognosis of nasopharyngeal carcinoma 48 .…”

Section: Resultsmentioning

confidence: 99%

Virus-host protein co-expression networks reveal temporal organization and strategies of viral infection

Aguirre,

Guantes

2023

Preprint

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Viral replication is a complex dynamical process involving the global remodelling of the host cellular machinery across several stages. In this study, we provide a unified view of the virus-host interaction at the proteome level reconstructing protein co-expression networks from quantitative temporal data of four large DNA viruses. We take advantage of a formal framework, the theory of interacting networks, to describe the viral infection as a dynamical system taking place on a network of networks where perturbations induced by viral proteins spread to hijack the host proteome for the virus benefit. Our methodology demonstrates how the viral replication cycle can be effectively examined as a complex interaction between protein networks, providing useful insights into the viral and host temporal organization and strategies, key protein nodes targeted by the virus and dynamical bottlenecks during the course of the infection.

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Section: Resultsmentioning

confidence: 99%

Virus-host protein co-expression networks reveal temporal organization and strategies of viral infection

Aguirre,

Guantes

2023

Preprint

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“…EB virus played some important negative role in relapse survival for Luminal type breast cancer (ER positive or PR positive breast cancer) in our study. There is little study researched the relationship between EBV and the ER for breast cancer but some are explored in the context of nasopharyngeal carcinoma (NPC) 27 . EBV infection in most associated tumors is latent, but the BZLF1 gene product, ZEBRA, can switch the infection from latent to lytic.…”

Section: Discussionmentioning

confidence: 99%

Role of Epstein-Barr Virus in Breast Cancer: Correlation with Clinical Outcome and Survival Analysis

Hsu,

Tsai,

et al. 2024

J. Cancer

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Background: Breast cancer is the most prevalent cancer among women worldwide. The potential involvement of Epstein-Barr virus (EBV) in breast cancer pathogenesis has been a subject of debate, but its correlation with clinical outcomes remains uncertain. Methods: In this study, we collected 276 pathologically confirmed breast cancer tissue samples from the tissue bank of MacKay Memorial Hospital and the National Health Research Institutes in Taiwan. DNA was extracted from frozen tissue using The QIAamp DNA Mini Kit. The Taqman quantitative PCR method was employed to assess the EBV copy number per cell in these samples, using NAMALWA cells as a reference. We performed statistical analyses, including 2 × 2 contingency tables, Cox regression analysis, and Kaplan-Meier survival curves, to explore the association between clinicopathologic factors and survival outcomes in breast cancer patients. We analyzed both relapse survival, which reflects the period patients remain free from cancer recurrence post-treatment, and overall survival, which encompasses all-cause mortality. Results: Our results revealed a significant association between EBV status and relapse survival (hazard ratio: 2.75, 95% CI: 1.30, 5.86; p = 0.008) in breast cancer patients. However, no significant association was found in overall survival outcomes. Additionally, we observed significant associations between ER status and tumor histologic grade with both overall and relapse survival. Patients with EBV-positive tumors exhibited higher recurrence rates compared to those with EBV-negative tumors. Furthermore, we noted significant correlations between EBV status and HER-2 (p = 0.0005) and histological grade (p = 0.02) in our cohort of breast cancer patients. Conclusions: The presence of EBV in breast cancer tumors appears to exert an impact on patient outcomes, particularly concerning recurrence rates. Our findings highlight the significance of considering EBV status as a potential prognostic marker in breast cancer patients. Nonetheless, further research is essential to elucidate the underlying molecular mechanisms and develop novel therapeutic approaches.

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“…We previously developed mRNA expression sequencing data of NPC samples using publicly available data from the GEO (Gene Expression Omnibus) database 17 . Briefly, the AOE (All Of gene expression) database was used to query all publicly available data regarding NPC (https://aoe.dbcls.jp) using the keywords “nasopharyngeal carcinoma” or “nasopharyngeal cancer.” After the review, four datasets (131 NPCs, four normal nasal mucosa and three NAT surrounding NPC) were utilized in our study.…”

Section: Methodsmentioning

confidence: 99%

“…EBV-negative nasopharyngeal carcinoma cell line, NPC/HK1 was reinfected with EBV using neomycin resistant (neo r ) EBV-infected Akata cells and green fluorescent protein (eGFP) neo r EBV-infected Akata cells, respectively, as described previously. 17,18 NPC/HK1-EBV-NeoR cells were prepared using neo r EBV-infected Akata cells. NPC/HK1-EBV-eGFP cells were prepared using eGFP-neo r EBVinfected Akata cells.…”

Section: Ebv Infection To Npc Cell Linesmentioning

confidence: 99%

Peritumoral SPARC expression induced by exosomes from nasopharyngeal carcinoma infected Epstein‐Barr virus: A poor prognostic marker

Dochi,

Kondo,

Komura

et al. 2023

Intl Journal of Cancer

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Epstein‐Barr virus (EBV)‐associated nasopharyngeal carcinoma (NPC) cells have high metastatic potential. Recent research has revealed that the interaction of between tumor cells and the surrounding stroma plays an important role in tumor invasion and metastasis. In this study, we showed the prognostic value of expression of SPARC, an extracellular matrix protein with multiple cellular functions, in normal adjacent tissues (NAT) surrounding NPC. In the immunohistochemical analysis of 51 NPC biopsy specimens, SPARC expression levels were significantly elevated in the NAT of EBER (EBV‐encoded small RNA)‐positive NPC compared to that in the NAT of EBER‐negative NPC. Moreover, increased SPARC expression in NAT was associated with a worsening of overall survival. The enrichment analysis of RNA‐seq of publicly available NPC and NAT surrounding NPC data showed that high SPARC expression in NPC was associated with epithelial mesenchymal transition promotion, and there was a dynamic change in the gene expression profile associated with interference of cellular proliferation in NAT, including SPARC expression. Furthermore, EBV‐positive NPC cells induce SPARC expression in normal nasopharyngeal cells via exosomes. Induction of SPARC in cancer‐surrounding NAT cells reduced intercellular adhesion in normal nasopharyngeal structures and promoted cell competition between cancer cells and normal epithelial cells. These results suggest that epithelial cells loosen their own binding with the extracellular matrix as well as stromal cells, facilitating the invasion of tumor cells into the adjacent stroma by activating cell competition. Our findings reveal a new mechanism by which EBV creates a pro‐metastatic microenvironment by upregulating SPARC expression in NPC.

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Estrogen induces the expression of EBV lytic protein ZEBRA, a marker of poor prognosis in nasopharyngeal carcinoma

Cited by 13 publications

References 50 publications

Virus-host protein co-expression networks reveal temporal organization and strategies of viral infection

Virus-host protein co-expression networks reveal temporal organization and strategies of viral infection

Role of Epstein-Barr Virus in Breast Cancer: Correlation with Clinical Outcome and Survival Analysis

Peritumoral SPARC expression induced by exosomes from nasopharyngeal carcinoma infected Epstein‐Barr virus: A poor prognostic marker

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