Ferroptosis is a newly recognized mechanism of regulated cell death. It was reported to be highly associated with immune therapy and chemotherapy. However, its mechanism of regulation in the tumor microenvironment (TME) and influence on oral squamous cell carcinoma (OSCC) therapy are unknown. We identified a ferroptosis-specific gene-expression signature, an FPscore, developed by a principal component analysis (PCA) algorithm to evaluate the ferroptosis regulation patterns of individual tumor. Multi-omics analysis of ferroptosis regulation patterns was conducted. Three distinct ferroptosis regulation subtypes, which linked to outcomes and the clinical relevance of each patient, were established. A high FPscore of patients with OSCC was associated with a favorable prognosis, a ferroptosis-related immune-activation phenotype, potential sensitivities to the chemotherapy and immunotherapy. Importantly, a high FPscore correlated with a low gene copy number burden and high immune checkpoint expressions. We validated the prognostic value of the FPscore using independent immunotherapy and pan-cancer cohorts. Comprehensive evaluation of individual tumors with distinct ferroptosis regulation patterns provides new mechanistic insights, which may be clinically relevant for the application of combination therapies in OSCC.

中文翻译：

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口腔鳞状细胞癌患者铁死亡调节模式和肿瘤微环境特征的多组学分析

铁死亡是一种新认识的调节细胞死亡的机制。据报道，它与免疫治疗和化疗高度相关。然而，其在肿瘤微环境（TME）中的调节机制以及对口腔鳞状细胞癌（OSCC）治疗的影响尚不清楚。我们确定了铁死亡特异性基因表达特征，即 FPscore，它是通过主成分分析 (PCA) 算法开发的，用于评估个体肿瘤的铁死亡调节模式。对铁死亡调节模式进行了多组学分析。建立了三种不同的铁死亡调节亚型，它们与每个患者的结果和临床相关性相关。OSCC 患者的高 FP 分数与良好的预后、铁死亡相关的免疫激活表型、对化疗和免疫治疗的潜在敏感性相关。重要的是，高 FPscore 与低基因拷贝数负担和高免疫检查点表达相关。我们使用独立免疫疗法和泛癌队列验证了 FPscore 的预后价值。对具有不同铁死亡调节模式的个体肿瘤的综合评估提供了新的机制见解，这可能与口腔鳞癌联合疗法的应用具有临床相关性。