Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Otolaryngology - Head & Neck Surgery, National University of Singapore, Singapore.
Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Oral Oncol. 2024 Oct;157:106941. doi: 10.1016/j.oraloncology.2024.106941. Epub 2024 Jul 17.
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) and keratinization (NES = 2.42, p = 6.95x10). In contrast, NPC tumors without the V317M substitution demonstrated increased immune-related processes, including cell activation (NES = 1.85, p = 8.29x10), myeloid leukocyte activation (NES = 2.16, p = 6.51x10) and leukocyte mediated immunity (NES = 1.99, p = 1.05x10). 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.
鼻咽癌（NPC）与 Epstein-Barr 病毒感染（EBV）密切相关。尽管 EBV 在全球范围内广泛存在，但 NPC 在华南和东南亚地区具有独特的地理分布。这种观察到的现象可以归因于不同 EBV 感染株与宿主遗传和环境因素的相互作用。BALF2 基因上的多态性已被证明会影响 NPC 的风险。值得注意的是，两个非同义 EBV 多态性（162476T>C、163364C>T）占流行地区 NPC 风险的大部分。这些多态性导致 BALF2 蛋白内的氨基酸变化（I1613V、V317M）。然而，它们对 NPC 肿瘤生物学的影响尚不清楚。我们评估了五个独立基因组数据集（包含 351 个 NPC 临床样本）中 BALF2 风险多态性的分布，证实了 NPC 中高危 EBV 株的高流行率。重要的是，我们观察到根据 EBV 风险株对肿瘤进行分组时，基于基因表达谱可将肿瘤分为两个具有不同生物学特征的组。具有 V317M 取代的 NPC 肿瘤显示出增加的增殖过程，包括细胞周期（NES=1.71，p=5.64x10）和角化（NES=2.42，p=6.95x10）。相比之下，不具有 V317M 取代的 NPC 肿瘤则显示出增加的免疫相关过程，包括细胞激活（NES=1.85，p=8.29x10）、髓样白细胞激活（NES=2.16，p=6.51x10）和白细胞介导的免疫（NES=1.99，p=1.05x10）。这些发现进一步深入了解了 BALF2 变体对 NPC 肿瘤生物学的影响。EBV 风险株可能有潜力定义 NPC 中具有生物学重要性的组。
