Zhu Jingjuan, Xu Xiao, Jiang Man, Yang Fangfang, Mei Yingying, Zhang Xiaochun
Cancer Precision Medical Center, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China.
Qingdao Medical College, Qingdao University, Qingdao, China.
Front Oncol. 2023 Mar 27;13:1145380. doi: 10.3389/fonc.2023.1145380. eCollection 2023.
Ferroptosis is a type of regulatory cell death (RCD) mode that depends on iron-mediated oxidative damage. It has the potential to improve the efficacy of tumor immunotherapy by modulating the tumor microenvironment (TME). Currently, immunotherapy has significantly improved the overall treatment strategy for advanced hepatocellular carcinoma (HCC), but the distinct immune microenvironment and high tolerance to the immune make massive differences in the immunotherapy effect of HCC patients. As a result, it is imperative to classify HCC patients who may benefit from immune checkpoint therapy. Simultaneously, the predictive value of ferroptosis in HCC and its potential role in TME immune cell infiltration also need to be further clarified.
Three ferroptosis molecular models were built on the basis of mRNA expression profiles of ferroptosis-related genes (FRGs), with notable variations in immunocyte infiltration, biological function, and survival prediction. In order to further investigate the predictive impact of immunotherapy response in HCC patients, the ferroptosis score was constructed using the principal component analysis (PCA) algorithm to quantify the ferroptosis molecular models of individual tumors.
In HCC, there were three totally different ferroptosis molecular models. The ferroptosis score can be used to assess genetic variation, immunotherapy response, TME characteristics, and prognosis. Notably, tumors with low ferroptosis scores have extensive tumor mutations and immune exhaustion, which are associated with a poor prognosis and enhanced immunotherapy response.
Our study indicates that ferroptosis plays an indispensable role in the regulation of the tumor immune microenvironment. For HCC, the ferroptosis score is an independent prognostic indicator. Assessing the molecular model of ferroptosis in individual tumors will assist us in better understanding the characteristics of TME, predicting the effect of immunotherapy in HCC patients, and thus guiding a more reasonable immunotherapy program.
铁死亡是一种依赖铁介导的氧化损伤的调节性细胞死亡（RCD）模式。它有潜力通过调节肿瘤微环境（TME）来提高肿瘤免疫治疗的疗效。目前，免疫疗法显著改善了晚期肝细胞癌（HCC）的整体治疗策略，但不同的免疫微环境和对免疫的高耐受性使得HCC患者的免疫治疗效果存在巨大差异。因此，对可能从免疫检查点治疗中获益的HCC患者进行分类势在必行。同时，铁死亡在HCC中的预测价值及其在TME免疫细胞浸润中的潜在作用也需要进一步阐明。
基于铁死亡相关基因（FRG）的mRNA表达谱构建了三种铁死亡分子模型，在免疫细胞浸润、生物学功能和生存预测方面存在显著差异。为了进一步研究免疫治疗反应对HCC患者的预测影响，使用主成分分析（PCA）算法构建铁死亡评分，以量化个体肿瘤的铁死亡分子模型。
在HCC中，存在三种完全不同的铁死亡分子模型。铁死亡评分可用于评估基因变异、免疫治疗反应、TME特征和预后。值得注意的是，铁死亡评分低的肿瘤具有广泛的肿瘤突变和免疫耗竭，这与预后不良和免疫治疗反应增强相关。
我们的研究表明，铁死亡在肿瘤免疫微环境的调节中起着不可或缺的作用。对于HCC，铁死亡评分是一个独立的预后指标。评估个体肿瘤的铁死亡分子模型将有助于我们更好地了解TME的特征，预测HCC患者的免疫治疗效果，从而指导更合理的免疫治疗方案。
