Background: Oropharyngeal squamous cell carcinoma (OPSCC) is a major subtype of head and neck cancer, with prognosis increasingly influenced by the tumour immune microenvironment. Although immune checkpoint inhibitors have improved outcomes for some patients, reliable predictive biomarkers remain limited. Methods: This study aimed to investigate the prognostic relevance and epigenetic regulation of natural killer T (NKT)-cell-related gene signatures in OPSCC. Clinicopathological and transcriptomic data from 81 OPSCC patients were analysed using single-sample gene set enrichment analysis (ssGSEA) to evaluate immune-related gene set enrichment scores. Associations with overall survival and clinical features were assessed, and candidate prognostic genes were further explored through expression, methylation, and network analyses. Results: High NKT cell differentiation enrichment scores were significantly associated with improved survival and favourable clinical features. Gene-level analyses identified ITK, ZNF683, and ATF2 as key prognostic markers linked to T-cell signalling and epigenetic regulation. Methylation profiling revealed hypermethylation of ITK and hypomethylation of ZNF683 in tumour tissues, suggesting an epigenetic basis for altered gene expression. Conclusions: These findings highlight NKT cell differentiation as a strong prognostic indicator in OPSCC and support further exploration of epigenetic–immunologic interactions as potential therapeutic targets.
背景：口咽鳞状细胞癌（OPSCC）是头颈部癌症的主要亚型，其预后日益受到肿瘤免疫微环境的影响。尽管免疫检查点抑制剂已改善部分患者的治疗结果，但可靠的预测性生物标志物仍然有限。方法：本研究旨在探讨自然杀伤T（NKT）细胞相关基因特征在OPSCC中的预后相关性及表观遗传调控机制。通过单样本基因集富集分析（ssGSEA）对81例OPSCC患者的临床病理学及转录组数据进行分析，评估免疫相关基因集的富集评分。进一步分析其与总生存期及临床特征的关联，并通过表达、甲基化及网络分析深入探究候选预后基因。结果：高NKT细胞分化富集评分与改善的生存率及良好临床特征显著相关。基因层面分析确定ITK、ZNF683和ATF2为与T细胞信号传导及表观遗传调控相关的关键预后标志物。甲基化谱分析显示肿瘤组织中ITK呈高甲基化状态，而ZNF683呈低甲基化状态，提示基因表达改变存在表观遗传学基础。结论：这些发现表明NKT细胞分化是OPSCC的重要预后指标，并支持进一步探索表观遗传-免疫相互作用作为潜在治疗靶点。
肿瘤(癌症)患者之家