基于生物信息学分析和实验验证筛选影响肝癌患者预后的铁死亡调控基因
Screening of ferroptosis-related genes affecting the prognosis of hepatocellular carcinoma patients based on bioinformatics analysis and experimental validation
摘要
Abstract
Objective:To screen ferroptosis-related genes(FRGs)affecting the prognosis of hepatocellular carcinoma patients based on bioinformatics technology.and validate them at cellular and tissue levels.Methods:Gene expression and clinical datasets of hepatocellular carcinoma were downloaded from TCGA database,and iron death-related genes were obtained from ferrdb data-base.LASSO regression analysis was used to construct a risk-proportional model and to compare patients'1-,2-,and 3-year sur-vival rates by receiver operating characteristic curves(ROC),and independent prognostic factors for hepatocellular carcinoma were screened using univariate and multivariate COX survival analyses.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed for FRGs associated with liver cancer prognosis.Final immune cell and immune function-related scores were performed.The resultant maps of immunohistochemistry of normal liver tissues and hepa-tocellular carcinoma tissues were downloaded from the Human Gene Protein Data Bank for hepatocellular carcinoma prognosis re-lated FRGs.Moreover the expression of TOP20 gene was compared by qPCR analysis in normal hepatocyte L02 and hepatocellu-lar carcinoma cell HepG2,clinically obtained hepatocellular carcinoma tissues and Para cancerous tissues of six hepatocellular carci-noma patients surgically resected.Results:A total of 42 differential FRGs affecting the prognosis of hepatocellular carcinoma pa-tients were obtained by analysis.eleven FRGs(G6PD,HRAS,SLC1A5,etc.)were finally screened by LASSO regression anal-ysis to construct a risk model for hepatocellular carcinoma patients.The survival analysis revealed that the survival rate of patients in the high-risk group was significantly lower than that of the low-risk group,and the immune score of patients in the high-risk group was significantly higher than that of the low-risk group.Tumor stage and risk value can be used as independent prognostic factors for hepatocellular carcinoma patients.Enrichment analysis revealed that relevant FRGs were mainly involved in biological functions such as cell cycle and lipid oxidation.Conclusion:FRGs can influence the prognosis of hepatocellular carcinoma pa-tients,which may be achieved by participating in the regulation of oxidative metabolism and immune microenvironment of tumor cells.关键词
肝癌/生物信息学/铁死亡Key words
Bioinformatics/Ferroptosis/HCC分类
医药卫生引用本文复制引用
姜宇朗,王铮,孙明瑜..基于生物信息学分析和实验验证筛选影响肝癌患者预后的铁死亡调控基因[J].海南医学院学报,2024,30(9):674-682,9.基金项目
This study was supported by the Fourth Batch of Traditional Chinese Medicine Talent Projects of the State Administration of Traditional Chinese Medicine(2017-124) （2017-124）
Shanghai Science and Technology Innovation Action Plan(119401972300) （119401972300）
Shandong Province 2021 Key R&D Plan(Major Science and Technology Innovation Project)(2021CXGC010509) （Major Science and Technology Innovation Project）
Key Discipline of Traditional Chinese Medicine Hepatobiliary Disease,Key Laboratory of Chronic Liver Disease Deficiency and Damage,and Shanghai Key Clinical Laboratory of Traditional Chinese Medicine of the State Administration of Traditional Chinese Medicine(14DZ2273200)(20DZ2272200) 国家中医药管理局第四批中医优才项目(2017-124) （14DZ2273200）
上海市科技创新行动计划(19401972300) （19401972300）
山东省2021年重点研发计划(重大科技创新工程)(2021CXGC010509) （重大科技创新工程）
国家中医药管理局中医肝胆病重点学科、慢性肝病虚损重点研究室和上海市中医临床重点实验室资助(14DZ2273200)(20DZ2272200) （14DZ2273200）
