摘要
[目的]基于生物信息学方法和体外实验,筛选与结肠癌相关的铁死亡基因,建立结肠癌风险预后模型。[方法]基于TCGA数据库和FerrDB数据库对结肠癌中的铁死亡相关基因进行Cox回归分析和LASSO回归分析,构建预后风险模型。Kaplan-Meier生存曲线分析和受试者工作特征(ROC)曲线分析验证预后模型的准确性,并对高低风险组患者的差异基因进行蛋白质-蛋白质相互作用(PPI)分析和功能富集分析。最后,通过体外实验验证PLIN4对结肠癌细胞HT29的生物功能,进一步验证预后模型的准确性。[结果]构建了以7个铁死亡基因(PLIN4、CXCL2、CAV1、MIOX、CDKN2A、AURKA、CDO1)为特征的结肠癌预后模型。Kaplan-Meier生存曲线分析和ROC曲线分析表明该模型具有良好的预测能力。高低风险组患者的差异基因可能涉及FN1等多个基因以及细胞粘附分子、血管平滑肌收缩、Wnt信号通路等多条信号途径。体外实验结果显示:下调PLIN4表达可显著抑制结肠癌细胞的增殖能力,促进结肠癌细胞铁死亡的发生。[结论]该预后模型能够准确预测结肠癌患者的预后,下调PLIN4的表达可促进结肠癌细胞铁死亡。
[Objective]To identify ferroptosis genes associated with colon cancer based on bioinformatics methods and in vitro experiments, and to establish a prognostic model for colon cancer risk.[Method]First, Cox regression analysis and LASSO regression analysis were performed to construct prognostic risk models based on the TCGA database and FerrDB database for ferroptosis-related genes in colon cancer.The accuracy of the prognostic model was verified using Kaplan-Meier survival curve analysis and receiver operating characteristic(ROC) curve analysis, and protein-protein interaction(PPI) analysis and functional enrichment analysis were performed for differential genes in high and low risk groups.Finally, the accuracy of the prognostic model was further validated by in vitro experiments to verify the biological function of PLIN4 on HT29 cells.[Result]A prognostic model for colon cancer featuring seven ferroptosis genes(PLIN4,CXCL2,CAV1,MIOX,CDKN2A,AURKA,CDO1) was constructed.Kaplan-Meier survival curve analysis and ROC curve analysis showed that the prognostic model had good predictive ability.The differential genes in the high and low risk groups may involve several genes such as FN1 and multiple signaling pathways such as cell adhesion molecules, vascular smooth muscle contraction, and Wnt signaling pathway.The results of in vitro experiments showed that down-regulation of PLIN4 expression significantly inhibited the proliferation ability of colon cancer cells and promoted the development of ferroptosis in colon cancer cells.[Conclusion] The prognostic model was able to accurately predict the prognosis of colon cancer patients.Down-regulation of PLIN4 expression promotes ferroptosis in colon cancer cells.
作者
杨丰帅
彭玲
邱东达
杨运泉
陈石林
周厚吾
YANG Fengshuai;PENG Ling;QIU Dongda;YANG Yunquan;CHEN Shilin;ZHOU Houwu(Department of Gastrointestinal Surgery,The First Hospital of Changsha,Changsha 410005,China;Department of Surgical Nursing,The First Hospital of Changsha,Changsha 410005,China)
出处
《生物技术》
CAS
2024年第4期439-447,共9页
Biotechnology
基金
长沙市2020年度科学技术局指导性科技计划项目(kzd2001091)
湖南省卫生健康委科研基金项目(202114021125)。
