Impact of high-risk EBV strains on nasopharyngeal carcinoma gene expression.

Autor: Lim CY; Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Otolaryngology - Head & Neck Surgery, National University of Singapore, Singapore., Ng GWY; Yong Loo Lin School of Medicine, National University of Singapore, Singapore., Goh CK; Department of Otolaryngology - Head & Neck Surgery, National University of Singapore, Singapore., Lee MKC; Department of Head and Neck and Thoracic Oncology, Division of Radiation Oncology, National Cancer Centre, Singapore., Cheong I; Temasek Life Sciences Laboratory, Singapore; Department of Biological Sciences, National University of Singapore, Singapore., Ooi EE; Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore., Liu J; Human Genomics, Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore., West RB; Department of Pathology, Stanford University School of Medicine, USA., Loh KS; Department of Otolaryngology - Head & Neck Surgery, National University of Singapore, Singapore., Tay JK; Department of Otolaryngology - Head & Neck Surgery, National University of Singapore, Singapore; Synthetic Biology Translational Research Programme, National University of Singapore, Singapore. Electronic address: joshtay@nus.edu.sg.
Jazyk: angličtina
Zdroj: Oral oncology [Oral Oncol] 2024 Oct; Vol. 157, pp. 106941. Date of Electronic Publication: 2024 Jul 17.
DOI: 10.1016/j.oraloncology.2024.106941
Abstrakt: Nasopharyngeal carcinoma (NPC) is closely associated with Epstein-Barr Virus infection (EBV). Despite ubiquitous EBV infection worldwide, NPC displays a unique geographical distribution in Southern China and Southeast Asia. This observed phenomenon can be attributed to the interplay of different strains of EBV infection with host genetics and environmental factors. Polymorphisms on the EBV BALF2 gene have been shown to influence risk of nasopharyngeal carcinoma (NPC). Notably, two non-synonymous EBV polymorphisms (162476T>C, 163364C>T) account for majority of NPC risk in endemic regions. These polymorphisms confer amino acid changes (I1613V, V317M) within the BALF2 protein. However, their impact on NPC tumor biology is unknown. We evaluated the distribution of BALF2 risk polymorphisms in five independent genomic datasets comprising 351 NPC clinical samples, confirming the high prevalence of high-risk EBV strains in NPC. Importantly, we observed two biologically distinct groups of tumors based on their gene expression profiles when grouped by their EBV risk strains. NPC tumors with the V317M substitution demonstrated increased proliferation processes including cell cycle (NES = 1.71, p = 5.64x10 -24 ) and keratinization (NES = 2.42, p = 6.95x10 -17 ). In contrast, NPC tumors without the V317M substitution demonstrated increased immune-related processes, including cell activation (NES = 1.85, p = 8.29x10 -31 ), myeloid leukocyte activation (NES = 2.16, p = 6.51x10 -24 ) and leukocyte mediated immunity (NES = 1.99, p = 1.05x10 -23 ). These findings provide further insight on the influence of BALF2 variants on NPC tumor biology. EBV risk strains may have the potential to define biologically important groups in NPC.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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