生物信息学分析姜黄素与非小细胞肺癌预后的关系

Bioinformatics analysis of the relationship between curcumin and prognosis of non-small cell lung cancer

目的探讨姜黄素通过调节铁死亡相关基因表达影响非小细胞肺癌(NSCLC)患者预后的作用机制。方法采用50μmol/L姜黄素和等体积DMSO处理A549细胞24 h后进行转录组测序,对差异表达基因进行富集分析(GSEA)。将富集到的基因集进行蛋白质互作(PPI)分析并同时进行加权基因共表达网络分析(WGCNA),获得与铁死亡相关基因集和表达水平。采用癌症和肿瘤基因图谱(TCGA)数据库(https://portal.gdc.cancer.gov),获取NSCLC队列的癌组织与癌旁组织的转录组数据,及对应的临床、预后信息,该数据集共包含1017个患者样本和108个正常样本,与姜黄素处理的细胞转录组数据进行相互验证。结果WGCNA分析结果显示,brown4模块与PI3K-AKT-mTOR通路具有显著关系,而brown4模块基因和差异表达基因、铁死亡相关基因集分析显示,共23个交集基因。预后分析结果显示ACSL3、BACH1、FTH1、SLC11A2基因与NSCLC患者预后有关,而其在姜黄素处理前后中的表达存在显著差异。免疫浸润分析显示,巨噬细胞浸润水平与ACSL3、BACH1、SLC11A2呈正相关,与FTH1呈负相关。结论通过整合转录组学及TCGA公共数据库数据,发现姜黄素可通过干预铁死亡相关基因表达改善患者预后。

Objective To investigate the effect of curcumin on the prognosis of patients with non-small cell lung cancer(NSCLC)by regulating the expression of iron death related genes.Methods A549 cells were treated with 50μmol/L curcumin and equal volume DMSO for 24 h,then transcriptome sequencing was performed and differential expression gene enrichment analysis(GSEA)was performed.Protein interaction(PPI)analysis and weighted gene co-expression network(WGCNA)analysis were performed to obtain the gene set and expression level associated with iron death.Cancer and tumor genome(TCGA)database(https://portal.gdc.cancer.gov),for NSCLC queue tissue adjacent to carcinoma and transcriptome data,and the corresponding clinical and prognostic information,the sample data set contains 1017 patients and 108 normal samples,The transcriptome data treated with curcumin were mutually verified.Results WGCNA analysis showed that brown4 module was significantly correlated with PI3K-AKT-mTOR pathway,and brown4 module gene,differentially expressed gene and iron-death related gene set analysis showed a total of 23 intersection genes.The result of prognosis analysis showed that ACSL3,BACH1,FTH1 and SLC11A2 genes were related to the prognosis of NSCLC patients,and their expressions were significantly different before and after curcumin treatment.Immunoinfiltration analysis showed that macrophage infiltration level was positively correlated with ACSL3,BACH1 and SLC11A2,and negatively correlated with FTH1.Conclusion By integrating transcriptomics and TCGA public database data,curcumin can improve the prognosis of patients by interfering with the expression of genes related to iron death.