肝细胞癌铜死亡标志物SLC31A1、DBT的鉴定及化合物筛选

Identification and compound screening of copper-induced cell death-related genes SLC31A1 and DBT in hepatocellular carcinoma

探究铜死亡相关基因对肝细胞癌(hepatocellular carcinoma,HCC)的影响,并挖掘治疗HCC的活性成分。通过GEO数据库下载GSE84402数据集,获取肝癌差异表达基因,通过文献检索铜死亡相关基因,两者取交集获得肝癌相关铜死亡基因。进一步分析交集基因,使用UALCAN分析其差异表达,R语言分析其表达水平与临床的相关性,Kaplan-Meier Plortter分析其预后价值,HCMDB分析其与肝癌转移的关系,并使用THPA分析其与肝癌的病理关系。最后进行化合物预测与分子对接。结果表明,与正常组相比,铜死亡关键基因SLC31A1、DBT在肿瘤中表达水平下调,病理分析显示其蛋白在HCC组织中表达增加,且与临床相关性变量性别、肿瘤分期、淋巴结转移显著相关,其高表达与肝癌预后良好相关,其中SLC31A1低表达与肝癌向肾上腺、肺部转移显著相关。最后筛选出可能与SLC31A1、DBT结合的活性化合物,其中白藜芦醇、叶酸对接分数高。研究认为铜死亡相关基因SLC31A1、DBT在HCC的发生发展中起重要作用,为HCC的诊断及治疗药物研究提供了新思路。

This study aimed to investigate the effect of copper-induced cell death-related genes on hepatocellular carcinoma(HCC)and to explore active components for treating HCC.The GSE84402 dataset was downloaded from the Gene Expression Omnibus(GEO)database to obtain the differentially expressed genes associated with HCC,and copper-induced cell death-related genes were retrieved from past literature;the commonalities between the two were considered to obtain HCC-related copper-induced cell death genes.The genes in common were further analyzed for differential expression using the UALCAN(University of Alabama at Birmingham Cancer Data Analysis)portal,the correlation between their expression levels and clinical levels was analyzed using the R language,prognostic value was determined using the Kaplan-Meier plotter,their relationship with HCC metastasis was examined using the Human Cancer Metastasis Database(HCMDB),and their pathological relationship with HCC was explored using the Treponema pallidum hemagglutination test.Lastly,compound prediction and molecular docking were performed.The results showed that compared with the normal group,expression levels of the key copper-induced cell death genes SLC31A1 and DBT were downregulated in tumors,and pathological analysis showed that their proteins were increased in HCC tissues.In addition,these genes were significantly correlated with the clinical correlation variables of sex,tumor stage,and lymph node metastasis.Their high expression was correlated with a good HCC prognosis,whereas low expression of SLC31A1 was significantly correlated with the metastasis of HCC to the adrenal glands and lungs.Finally,the active compounds that may bind to SLC31A1 and DBT were screened,of which resveratrol and folic acid exhibited high docking scores.Hence,it could be concluded that copper-induced cell death-related genes SLC31A1 and DBT play an important role in the development of HCC,and this study provides new theories for the diagnosis of HCC and therapeutic drug research.