State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.
Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.
Int J Biol Sci. 2020 Jul 6;16(13):2430-2441. doi: 10.7150/ijbs.45050. eCollection 2020.
Hepatocellular carcinoma (HCC) is a highly heterogeneous disease, which makes the prognostic prediction challenging. Ferroptosis, an iron-dependent form of regulated cell death, can be induced by sorafenib. However, the prognostic value of ferroptosis-related genes in HCC remains to be further elucidated. In this study, the mRNA expression profiles and corresponding clinical data of HCC patients were downloaded from public databases. The least absolute shrinkage and selection operator (LASSO) Cox regression model was utilized to construct a multigene signature in the TCGA cohort. HCC patients from the ICGC cohort were used for validation. Our results showed that most of the ferroptosis-related genes (81.7%) were differentially expressed between HCC and adjacent normal tissues in the TCGA cohort. Twenty-six differentially expressed genes (DEGs) were correlated with overall survival (OS) in the univariate Cox regression analysis (all adjusted < 0.05). A 10-gene signature was constructed to stratify patients into two risk groups. Patients in the high-risk group showed significantly reduced OS compared with patients in the low-risk group ( < 0.001 in the TCGA cohort and = 0.001 in the ICGC cohort). The risk score was an independent predictor for OS in multivariate Cox regression analyses (HR> 1, < 0.01). Receiver operating characteristic (ROC) curve analysis confirmed the signature's predictive capacity. Functional analysis revealed that immune-related pathways were enriched, and immune status were different between two risk groups. In conclusion, a novel ferroptosis-related gene signature can be used for prognostic prediction in HCC. Targeting ferroptosis may be a therapeutic alternative for HCC.
肝细胞癌 (HCC) 是一种高度异质性疾病，这使得预后预测具有挑战性。索拉非尼可以诱导铁依赖性的细胞死亡形式——铁死亡。然而，铁死亡相关基因在 HCC 中的预后价值仍有待进一步阐明。在本研究中，从公共数据库下载了 HCC 患者的 mRNA 表达谱和相应的临床数据。利用最小绝对收缩和选择算子 (LASSO) Cox 回归模型在 TCGA 队列中构建了一个多基因特征。使用 ICGC 队列中的 HCC 患者进行验证。我们的结果表明，在 TCGA 队列中，大多数铁死亡相关基因（81.7%）在 HCC 和相邻正常组织之间存在差异表达。在单因素 Cox 回归分析中，有 26 个差异表达基因（DEGs）与总生存期（OS）相关（所有调整后<0.05）。构建了一个 10 基因特征来将患者分为两个风险组。与低风险组相比，高风险组患者的 OS 明显降低（TCGA 队列中<0.001，ICGC 队列中=0.001）。风险评分在多因素 Cox 回归分析中是 OS 的独立预测因子（HR>1，<0.01）。受试者工作特征（ROC）曲线分析证实了该特征的预测能力。功能分析表明，免疫相关途径被富集，并且两个风险组之间的免疫状态不同。总之，一个新的铁死亡相关基因特征可用于 HCC 的预后预测。靶向铁死亡可能是 HCC 的一种治疗选择。
