铁死亡通路关键基因在肝癌中的表达及临床意义

肝脏 ›› 2023, Vol. 28 ›› Issue (6): 660-664.

铁死亡通路关键基因在肝癌中的表达及临床意义

王晓, 张凌云

201104 上海市老年医学中心肿瘤内科;复旦大学附属中山医院肿瘤内科

收稿日期:2023-02-25 出版日期:2023-06-30 发布日期:2023-08-30
通讯作者: 张凌云,Email:zhanglingyunyiya＠163.com

Expression and clinical significance of key genes of iron death pathway in liver cancer

WANG Xiao^1,2, ZHANG Ling-yun^1,2

1. Department of Medical Oncology, Shanghai Geriatric Medical Center, Shanghai 201104,China;
2. Department of Medical Oncology, Zhongshan Hospital of Fudan University, Shanghai 200032,China

Received:2023-02-25 Online:2023-06-30 Published:2023-08-30
Contact: ZHANG Ling-yun,Email:zhanglingyunyiya＠163.com

摘要/Abstract

摘要： 目的通过生物信息学分析铁死亡通路关键基因在肝癌中的表达、预后价值,及其与免疫微环境的相关性。方法利用GEPIA在线数据库分析铁死亡通路关键基因在肝癌中的表达;采用cBioPortal在线数据库分析肝癌患者中铁死亡通路关键基因的基因改变情况,Kaplan-Meier生存曲线分析其与肝癌患者预后的关系,采用TIMER数据库及TIDE数据库分析铁死亡通路关键基因与免疫环境的相关性。结果通过GEPIA数据库发现ACSL4在肝癌组织中的mRNA表达量明显高于正常组织(P<0.05)。cBioPortal数据库分析显示肝癌中铁死亡通路关键基因存在基因改变,主要包括基因扩增、缺失突变、错义突变和框内突变。Kaplan-Meier生存分析显示GPX4的高表达与肝癌患者预后良好相关(PFS: HR=0.68,P=0.014);SLC7A11的高表达与肝癌患者预后差相关(OS: HR=2.41,P=5.3e-07; PFS: HR=1.79,P=0.00043)。TIMER数据库分析显示SLC7A11和Nrf2与B细胞、CD8⁺T淋巴细胞、CD4⁺T淋巴细胞、中性粒细胞、巨噬细胞和树突状细胞的浸润均呈正相关。结论铁死亡通路关键基因与肝癌患者的预后、免疫细胞浸润存在显著相关性,是肝癌治疗的潜在靶点,具有重要的临床价值。

关键词: 肿瘤, 铁死亡通路, 基因, 免疫微环境

Abstract: Objective To investigate the expression and prognostic value of key iron death pathway genes in liver cancer and their correlation with the immune microenvironment by bioinformatics. Methods GEPIA online database was used to analyze the expression ferroptosis-related key genes in liver cancer. cBioPortal online database was used to analyze the gene mutation of ferroptosis-related key genes. Kaplan-Meier survival analysis was used to analyze the relationship between ferroptosis-related key genes and prognosis. The TIMER database and the TIDE database were used to analyze the correlation between key genes of the iron death pathway and the immune environment. Results The mRNA expression of ACSL4 was found to be significantly higher in liver cancer tissues than in normal tissues through the GEPIA database (P<0.05). cBioPortal database analysis revealed genetic alterations in key genes of iron death pathway in hepatocellular carcinoma, mainly including gene amplification, deletion mutations, missense mutations and in-frame mutations. Kaplan-Meier survival analysis showed that high GPX4 expression was associated with good prognosis (PFS:HR=0.68, P=0.014) and high expression of SLC7A11 was associated with poor prognosis (OS:HR=2.41, P=5.3e-07; PFS: HR=1.79, P=0.00043). TIMER database analysis showed that SLC7A11 and Nrf2 were positively correlated with infiltration of B cells, CD8⁺T lymphocytes, CD4⁺T lymphocytes, neutrophils, macrophages and dendritic cells. Conclusion Iron death pathway key genes are significantly correlated with prognosis and immune cell infiltration in patients with liver cancer, and are potential targets for treatment with important clinical value.

Key words: Liver camcer, Ferroptosis, Gene, Immune microenvironment

王晓, 张凌云. 铁死亡通路关键基因在肝癌中的表达及临床意义[J]. 肝脏, 2023, 28(6): 660-664.

WANG Xiao, ZHANG Ling-yun. Expression and clinical significance of key genes of iron death pathway in liver cancer[J]. Chinese Hepatolgy, 2023, 28(6): 660-664.

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