文献类型：期刊文献

中文题名：基于生物信息学未分化甲状腺癌LncRNA基因与免疫浸润机制及中药预测的研究

英文题名：LncRNA Genes and Immune Infiltration Mechanism and TCM Prediction in Undifferentiated Thyroid Cancer Based on Bioinformatics

作者：易希善[1];柏婷燕[1];肖国庆[1];杨维杰[2];王苑铭[2];康学东[2]

第一作者：易希善

机构：[1]甘肃中医药大学,甘肃兰州730000;[2]甘肃中医药大学附属医院,甘肃兰州730000

第一机构：甘肃中医药大学

年份：2024

卷号：51

期号：2

起止页码：6

中文期刊名：辽宁中医杂志

外文期刊名：Liaoning Journal of Traditional Chinese Medicine

收录：CSTPCD;;北大核心:【北大核心2023】；

基金：国家自然科学基金项目(8216150429)。

语种：中文

中文关键词：未分化甲状腺癌;生物信息学;长链非编码RNA;免疫浸润机制;中药预测

外文关键词：ATC;bioinformatics;LncRNA;immune infiltration mechanism;traditional Chinese medicine prediction

摘要：目的基于GEO数据库对未分化甲状腺癌基因数据进行差异分析、基因富集分析和免疫浸润分析,为深入了解未分化甲状腺癌免疫相关机制及治疗提供理论依据。方法利用GEO数据库检索有关ATC的芯片,根据样本数量及芯片类型,筛选出符合条件的芯片,借助R语言软件筛选出符合条件的差异基因,筛选ATC中差异表达的lncRNA,构建LncRNA-miRNA-mRNA网络图,并构建蛋白质-蛋白质相互作用关系网络(PPI)并进行GO富集分析和KEGG通路分析。同时利用CIBERSORT反卷积法对22种免疫细胞在未分化甲状腺癌中的浸润情况进行分析。并通过Coremine Medical进行治疗中药预测。结果经检索GEO数据库找到编码为GSE65144的基因芯片,利用R语言分析筛选出LncRNA差异基因127个,其中上调基因51个,下调基因76个,并对差异基因绘制ceRNA网络;将得出的LncRNA进行PPI网络分析,筛选出核心基因20个,排名靠前的有MYC、JUN、EGLN3、KIF23、YWHAH。GO富集分析显示其参与了RNA聚合酶Ⅱ启动子的转录调控、RNA聚合酶Ⅱ启动子转录的正调控、细胞增殖的正调控、细胞迁移的正调控等生物学过程,KEGG主要富集通路为癌症信号通路、MAPK信号通路、PI3K-AKT信号通路等。免疫浸润结果显示甲状腺未分化癌(anaplastic thyroid carcinoma,ATC)中巨噬细胞M0和巨噬细胞M2显著增高,而浆细胞和T细胞γ-δ显著减少。单核细胞和中性粒细胞呈显著正相关(r=0.90),活化的肥大细胞和中性粒细胞呈显著正相关(r=0.88),活化的肥大细胞和单核细胞呈显著正相关(r=0.72),嗜酸性粒细胞和CD_(4)T细胞呈显著正相关(r=0.72),T细胞γ-δ和滤泡辅助T细胞呈显著正相关(r=0.71)。并且,巨噬细胞M2和浆细胞呈显著负相关(r=-0.70),T细胞γ-δ和活化的树突状细胞呈显著负相关(r=-0.68),T细胞γ-δ和巨噬细胞M0呈显著负相关(r=-0.56)。预测中药主要集中在清热解毒药和补虚药,归经主要为肝、脾、肾经。结论ATC患者基因差异表达和免疫细胞浸润率的个体差异比较显著。在ATC肿瘤组织中具有高比例浸润的免疫细胞是其治疗的潜在目标。中药治疗是一个新的方向,有待后续的临床及基础实验加以验证。
Objective Based on the GEO database,differential analysis,gene enrichment analysis and immune infiltration analysis of anaplastic thyroid cancer gene data were performed to provide a theoretical basis for in-depth understanding and treatment of the immune-related mechanisms of anaplastic thyroid cancer.Methods The GEO database was used to search for chips related to ATC,screen out the qualified chips according to the number of samples and chip types,the qualified differential genes with the help of R language software and the differentially expressed lncRNAs in ATC,and build a LncRNA-miRNA-mRNA network Graph,and it constructed a protein-protein interaction network(PPI)and performed GO enrichment analysis and KEGG pathway analysis.At the same time,CIBERSORT deconvolution method was used to analyze the infiltration of 22 kinds of immune cells in anaplastic thyroid cancer.And the prediction of traditional Chinese medicine was performed by Coremine Medical.Results After searching the GEO database,the gene chip coded as GSE65144 was found,and 127 LncRNA differential genes were screened by R language analysis,including 51 up-regulated genes and 76 down-regulated genes,and the ceRNA network was drawn for the differential genes.Through network analysis,20 core genes were screened out,and the top ones were MYC,JUN,EGLN3,KIF23 and YWHAH.GO enrichment analysis showed that it was involved in the transcriptional regulation of RNA polymeraseⅡpromoter,the positive regulation of RNA polymeraseⅡpromoter transcription,the positive regulation of cell proliferation,the positive regulation of cell migration and other biological processes.KEGG main enrichment pathway included cancer signaling pathway,MAPK signaling pathway,PI3K-AKT signaling pathway,etc.The results of immune infiltration showed that macrophage M0 and macrophage M2 were significantly increased in ATC,while plasma cells and T cellsγ-δwere significantly decreased.There was a significant positive correlation between monocytes and neutrophils(r=0.90),a significant positive correlation between activated mast cells and neutrophils(r=0.88),and a significant positive correlation between activated mast cells and monocytes(r=0.72),eosinophils and CD_(4) T cells were significantly positively correlated(r=0.72),and T cellsγ-δand follicular helper T cells were significantly positively correlated(r=0.71).Furthermore,there was a significant negative correlation between macrophage M2 and plasma cells(r=-0.70),a significant negative correlation between T cellγ-δand activated dendritic cells(r=-0.68),and a significant negative correlation between T cellγ-δand macrophage phagocytosis M0 was significantly negatively correlated(r=-0.56).It is predicted that traditional Chinese drugs mainly focus on clearing heat and detoxifying drugs and tonifying deficiency drugs,with the main meridians being liver,spleen and kidney meridians.Conclusion The individual differences of gene differential expression and immune cell infiltration rate in ATC patients were significant.Cells with a high proportion of infiltrating cells in ATC tumor tissues are potential targets for their treatment.Traditional Chinese medicine treatment is a new treatment method,which needs to be verified by follow-up clinical and basic experiments.