Abstract:

Objective Hepatocellular carcinoma（HCC）is a leading cause of cancer mortality worldwide. This study was aimed atexploring the prognosis predictive ability of ferroptosis-related genes in HCC and constructing a reliable risk model for clinical management. The expression of ferroptosis-related genes in ischemia-reperfusion injury after liver transplantation was preliminarily studied. Methods Bioinformatics analysis of transcription data obtained from Therapeutically Applicable Research to Generate Effective Treatments（TARGET）was utilized in this study. COX regression and consensus clustering were performed to identify two molecular subgroups based on ferroptosis related to the prognosis of HCC patients. Furthermore，we explored the underlying mechanism of ferroptosis involved in the prognosis of HCC through the pathway analysis of the differentially expressed genes of the two molecular subsets. We then performed LASSO-COX regression analysis to build the risk model and visualize the model using a nomogram graph. Transcription data obtained from the GEO database was used to preliminarily explore the expression of ferroptosis-related genes in ischemiareperfusion injury after liver transplantation. Results We identified two molecular subgroups with distinct overall survival based on the different expression profiles of differentially expressed ferroptosis-related genes. Pathways analysisshowed 

differentially expressed immune and bile acid metabolism related genes between the two molecular subgroups. Finally，we established a risk model based on six ferroptosis-related genes KLF2，MYCN，FZD7，PRDX6，HILPDA，and SLC7A11. The nomogram established with the six genes performed reliable predictive ability of HCC prognosis. In addition，ferroptosis-related genes'expression was significantly changed in ischemia-reperfusion injury after liver transplantation. Conclusion The risk model developed based on the expression of ferroptosis related genes could act as a potent predictor of HCC prognosis.

Key words:

Hepatocellular carcinoma , Ferroptosis , Immune microenvironment , Prognosis , Liver transplantation

摘要：

目的 肝细胞癌（hepatocellular carcinoma，HCC）是全球癌症死亡的重要原因。本研究旨在探讨肝细胞癌中铁死亡相关基因的预后预测能力，构建基于铁死亡相关基因的风险预测模型，并初步研究铁死亡相关基因在肝移植缺血 / 再灌注损伤中的表达改变。 方法 本研究利用从 TARGET 数据库获得的转录数据进行生物信息学分析，采用 COX 回归和共识聚类法鉴定了 2 个基于铁死亡相关基因的肝细胞癌分子亚群。进一步通过对两个分子亚群差异表达基因的通路富集分析，探索铁死亡参与肝细胞癌预后的可能机制。然后，我们进行了LASSO-COX 回归分析，以建立风险预测模型，并评估模型的可靠性。通过对 GEO 数据库中转录组数据进行差异表达基因分析，初步探索肝移植缺血 / 再灌注损伤中铁死亡相关基因表达改变。 结果 我们根据铁死亡相关基因的不同表达谱确定了两个具有不同总生存期的肝细胞癌分子亚群。两个分子亚群之间差异表达基因通路富集到免疫和胆汁酸代谢相关通路。最终我们构建了基于 6 个铁死亡相关基因 KLF2、MYCN、FZD7、PRDX6、HILPDA、SLC7A11 的风险模型，并使用列线图进行模型的可视化，模型评估显示该模型对肝细胞癌患者的预后具有可靠的预测能力。另外，肝移植后缺血 / 再灌注损伤中铁死亡相关基因有明显的表达改变。 结论 基于铁死亡相关基因表达开发的风险模型可以较可靠地预测肝细胞癌预后。

关键词:

肝细胞癌 , 铁死亡 , 免疫微环境 , 预后 , 肝移植