The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang, 524023, Guangdong, China.
Southern Marine Science and Engineering Guangdong Laboratory (Zhanjiang), Zhanjiang, 524023, Guangdong, China.
Sci Rep. 2022 Jun 15;12(1):10007. doi: 10.1038/s41598-022-14554-7.
Ferroptosis is a novel type of cell death depending on iron and is strongly related to the development of tumors. Hepatocellular carcinoma (HCC) is a malignancy with high incidence. Despite some reports demonstrating the relation between ferroptosis-related genes and HCC, more details have not been excavated. In the present study, we collected and analyzed HCC patients' datasets from the TCGA-LIHC project and ICGC portal, respectively. Through the bioinformatic methods, we screened 126 differentially expressed genes. Then a prognostic model was established with four genes (GPX2, MT3, PRDX1, and SRXN1). PRDX1 is the hub gene of the prognosis model and has a high expression in hepatocellular carcinoma tumor tissue and cell lines. We further found that silencing PRDX1 increased the accumulation of ferrous ions and lipid peroxidation accumulation in HEPG2 cells and promoted ferroptosis in hepatocellular carcinoma. In conclusion, the study demonstrated the four-gene signature can be used to predict HCC prognosis. It also revealed the potential function of the ferroptosis-related gene PRDX1 in HCC, which can be a biomarker of the prediction for HCC outcome.
铁死亡是一种新型的依赖于铁的细胞死亡方式，与肿瘤的发生发展密切相关。肝细胞癌（HCC）是一种发病率较高的恶性肿瘤。尽管有一些报道表明铁死亡相关基因与 HCC 之间存在关系，但尚未挖掘出更多细节。在本研究中，我们分别从 TCGA-LIHC 项目和 ICGC 门户中收集和分析了 HCC 患者的数据集。通过生物信息学方法，我们筛选出了 126 个差异表达基因。然后，我们使用四个基因（GPX2、MT3、PRDX1 和 SRXN1）建立了一个预后模型。PRDX1 是预后模型的枢纽基因，在肝癌肿瘤组织和细胞系中高表达。我们进一步发现，沉默 PRDX1 会增加 HEPG2 细胞中铁离子的积累和脂质过氧化产物的积累，从而促进肝癌细胞发生铁死亡。总之，该研究表明，四基因特征可用于预测 HCC 的预后。它还揭示了铁死亡相关基因 PRDX1 在 HCC 中的潜在功能，可作为预测 HCC 结局的生物标志物。
