Liu Yang, Zhang Xi, Zhang Junjun, Tan Juan, Li Jie, Song Zewen
Department of Pathology, The Third Xiangya Hospital of Central South University, Changsha, China.
Department of Oncology, The Third Xiangya Hospital of Central South University, Changsha, China.
Front Cell Dev Biol. 2020 Dec 23;8:596679. doi: 10.3389/fcell.2020.596679. eCollection 2020.
Immunotherapy and sorafenib exert anti-tumor effects via ferroptosis, but reliable biomarkers for the individual treatment and prognosis prediction of hepatocellular carcinoma (HCC) based on the ferroptosis and immune status remain lacking.
Ferroptosis-related genes (FRGs) were identified by downloading data from FerrDb and by searching and reading original articles from PubMed. Immune-related genes (IRGs) were downloaded from ImmPort. Prognostic FRGs and IRGs in the GSE14520 ( = 220) and The Cancer Genome Atlas (TCGA, = 365) datasets were identified. Least absolute shrinkage and selection operator (LASSO) Cox regression and multivariate Cox regression were used for model construction. Ferroptosis expression profiles, the infiltration of immune cells, and the somatic mutation status were analyzed and compared.
Twenty-seven prognostic ferroptosis- and immune-related signatures were included to construct a comprehensive index of ferroptosis and immune status (CIFI). A subgroup of patients was identified as having a high CIFI value, which was associated with a worse prognosis. This subgroup of patients had significantly up-regulated expressions of many suppressors of ferroptosis and higher fractions of immunosuppressive cells, such as cancer-associated fibroblasts (CAFs) and myeloid-derived suppressor cells (MDSCs). Notably, somatic mutation analysis indicated that high-CIFI patients had higher levels of tumor heterogeneity and higher mutation frequencies of genes like TP53.
In this work, a novel prognostic classifier was developed based on ferroptosis- and IRGs in HCC, and this classifier could be used for prognostic prediction and the selection of patients for immunotherapies and targeted therapies.
免疫疗法和索拉非尼通过铁死亡发挥抗肿瘤作用，但基于铁死亡和免疫状态的用于肝细胞癌（HCC）个体治疗和预后预测的可靠生物标志物仍然缺乏。
通过从FerrDb下载数据以及搜索和阅读来自PubMed的原始文章来鉴定铁死亡相关基因（FRG）。从ImmPort下载免疫相关基因（IRG）。在GSE14520（n = 220）和癌症基因组图谱（TCGA，n = 365）数据集中鉴定预后FRG和IRG。使用最小绝对收缩和选择算子（LASSO）Cox回归和多变量Cox回归进行模型构建。分析并比较铁死亡表达谱、免疫细胞浸润和体细胞突变状态。
纳入27个预后性铁死亡和免疫相关特征以构建铁死亡和免疫状态综合指数（CIFI）。确定了一组CIFI值高的患者亚组，其与较差的预后相关。该患者亚组中许多铁死亡抑制因子的表达显著上调，并且免疫抑制细胞（如癌症相关成纤维细胞（CAF）和髓系来源的抑制细胞（MDSC））的比例更高。值得注意的是，体细胞突变分析表明，高CIFI患者具有更高水平的肿瘤异质性以及更高的TP53等基因突变频率。
在这项研究中，基于HCC中的铁死亡相关基因和IRG开发了一种新型预后分类器，该分类器可用于预后预测以及免疫疗法和靶向疗法患者的选择。
