生信分析鉴定青蒿素治疗非小细胞肺癌的铁死亡基因

Identification of ferroptosis genes associated with artemisinins for the treatment of non-small cell lung cancer through bioinformatics analysis

通过生物信息学分析,鉴定不同类型的青蒿素治疗非小细胞肺癌的相关铁死亡基因。通过在线数据库,对相关类型的青蒿素成分进行筛选和靶点预测。通过WGCNA和差异分析,获取非小细胞肺癌相关基因。通过PubMed数据库获取铁死亡相关基因。将三者进行取交集,得到治疗NSCLC相关的铁死亡基因。通过GO和KEGG功能富集分析,明确其作用机制。构建PPI蛋白互作网络筛选核心基因并进行生存分析。然后进行分子对接和免疫组化层面验证。结果表明:共筛选出不同类型的青蒿素5种,其靶点分别为103个,82个,71个,22个和112个。WGCNA分析筛选出了了9070个基因,差异分析鉴定了4276个差异表达基因。通过将上述二者与258个铁死亡基因取交集,得到了Artemetin治疗NSCLC铁死亡相关基因2个(CA9、PTGS2),其中:Artemisinin(1个),Artemisitene(1个),Deoxyartemisinin(0个)和Dihydroartemisinin(2个)。GO和KEGG功能富集分析显示,其发挥作用可能与组蛋白乙酰化有关,通过孕酮介导的细胞成熟途径通路起作用。PPI和生存分析显示AURKA,PLK1和TYMS在高低风险组之间具有显著性。分子对接结合显示AURKA与Dihydroartemisinin在对接结果中最优,其次是PLK1与Dihydroartemisinin,TYMS与Artemetin。HPA免疫组化验证了AURKA、PLK1和TYMS在腺癌/鳞癌中具有明显的表达差异。本研究鉴定了不同类型青蒿素治疗非小细胞肺癌相关的铁死亡基因,初步了解其发挥作用的机制,这有可能为青蒿素治疗非小细胞肺癌提供新的策略。

This research aims to identify the iron death genes related to different types of artemisinin in the treatment of non-small cell lung cancer through bioinformatics analysis.Screening and target prediction of related types of artemisinin components were conducted through online database.Non-small cell lung cancer related genes were obtained through WGCNA and difference analysis,while iron death-related genes were obtained through PubMed database.The intersection of the three was conducted to get the iron death gene related to the treatment of NSCLC.Through GO and KEGG functional enrichment analysis,the mechanism of action was clarified.A PPI protein interaction network was constructed to screen core genes and conduct survival analysis.Then molecular docking and immunohistochemistry level verification were performed.A total of five different types of Artemisinin were screened,and their targets were 103,82,71,22,and 112,respectively.WGCNA analysis screened out 9070 genes,and differential analysis identified 4276 differentially expressed genes.By intersecting the above two with 258 iron death genes,2 genes related to Artemetin treatment of NSCLC iron death were obtained,Artemisinin 1,Artemisitene 1,Deoxyartemisinin 0 and Dihydroartemisinin 2.The functional enrichment analysis of GO and KEGG shows that its function may be related to histone phosphorylation,which works through the Progesterone-mediated oocyte maturation pathway.PPI and survival analysis show that AURKA,PLK1 and TYMS are significant between the high and low risk groups.The functional enrichment analysis of GO and KEGG show that its function may be related to histone phosphorylation,which works through the Progesterone-mediated oocyte maturation pathway.PPI and survival analysis show that AURKA,PLK1 and TYMS are significant between the high and low risk groups.Molecular docking shows that AURKA and Dihydroartemisinin are the best in the docking results,followed by PLK1 and Dihydroartemisinin,and TYMS and Artemetin.HPA immunohistochemistry verifies that AURKA,PLK1 and TYMS have significant expression differences in adenocarcinoma/squamous cell carcinoma.This study has identified different types of Artemisinin-related iron death genes in the treatment of non-small cell lung cancer,and a preliminary understanding of the mechanism of its action may provide a new strategy for Artemisinin in the treatment of non-small cell lung cancer.