铁死亡相关风险评估模型在宫颈癌研究中的应用  

Application of ferroptosis-related risk assessment models in cervical cancer

作　　者：李培莉[1] 文丽芳[1] LI Pei-li;WEN Li-fang(Department of Obstetrics and Gynecology,Clinical Department,Fenyang,Shanxi Medical University,Fenyang 032200,Shanxi Province,China)

机构地区：[1]山西医科大学汾阳学院临床系妇产教研室,山西汾阳032200

出　　处：《中国临床药理学杂志》2024年第13期1953-1957,共5页The Chinese Journal of Clinical Pharmacology

基　　金：山西省科技创新计划基金资助项目(2022L672)。

摘　　要：目的构建铁死亡相关风险评估模型,探讨铁死亡对宫颈癌生存期的影响,并预测靶向的微小RNA(miRNA)。方法首先通过FerrDb、MSigDB数据库及已有的研究中定义一个新的铁死亡相关基因数据集,下载TCGA、GEO数据库中宫颈癌数据进行差异分析,筛选出差异表达(DE)的铁死亡相关基因。其次,用LASSO Cox回归分析构建风险评分模型,根据风险评分中位值将TCGA数据库中的宫颈癌患者分为高、低风险2组。用Kaplan-Meier分析、受试者工作曲线、临床病例特征以及免疫分析对评分模型预测进行评估。最后,通过miRDB、TargetScan、StarBase数据库预测潜在调控目的基因的miRNA。结果在宫颈癌组织中共获得28个DE铁死亡相关基因。高风险组患者的总体生存期更短(0.76年vs 1.00年,P<0.001),具有更高水平免疫抑制细胞的浸润。宫颈癌组织中铁死亡相关基因角鲨烯环氧化酶(SQLE)的表达显著升高。通过数据库预测得出,miR-579-3p可能调控SQLE的表达。结论本研究构建了用于预测宫颈癌预后的铁死亡基因风险评分模型,筛选出潜在的miRNA——miR-579-3p,调控宫颈癌组织中铁死亡相关基因SQLE的表达。Objective To develop a risk assessment model related to ferroptosis,to explore the effects of ferroptosis on cervical cancer survival,to obtain differentially expressed ferroptosis-related genes in cervical cancer,and to predict microRNAs(miRNAs)targeting genes.Methods First,a ferroptosis-related gene dataset was defined using FerrDb,the Molecular Signatures Database,and a collection of ferroptosis-related genes in existing studies.Cervical cancer data from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus databases were downloaded for differential analysis,and differentially expressed(DE)ferroptosis-related genes were screened out.Second,the risk score model was developed by least absolute shrinkage and selection operato regression analysis,and the cervical cancer data in the TCGA database were divided into two groups:high risk and low risk groups according to the score.The scoring model was evaluated by Kaplan-Meier analysis,subject working curves,clinical characteristics and immunoassays.Finally,miRNA for potential regulation of target genes was predicted by miRDB,TargetScan and starBase databases.Results A total of 28 DE ferroptosis-related genes were obtained in the cervical cancer data.The results showed that patients in the highrisk group had shorter overall survival(0.76 year vs 1.00 year,P<0.001)and higher levels of infiltration of immunosuppressive cell infiltration than those in the low-risk group.The expression of the ferroptosis-related gene SQLE was significantly increased in cervical cancer.Finally,through database prediction,miR-579-3p was found to be the potential regulator of the expression of squalene epoxidase(SQLE).Conclusion In this study,a risk scoring model of ferroptosis gene for predicting the prognosis of cervical cancer was developed,and the potential miRNA——miR-579-3p for regulating the expression of ferroptosis-related gene SQLE in cervical cancer was screened.

关 键 词：宫颈癌 铁死亡 微小RNA 角鲨烯环氧化酶 miR-579-3p 

分 类 号：R97[医药卫生—药品]