【摘要】 目的 通过基因表达数据分析与心房颤动(atrial fibrillation, AF)和结直肠癌(colorectal cancer, CRC)相关的关键基因(hub genes)。方法 数据来自基因表达综合数据库(Gene Expression Omnibus, GEO)的数据集GSE14975和GSE83889。使用Limma软件包筛选具有统计参数P<0.05和∣fold change(FC)∣>1的差异表达基因(differentially expressed genes, DEGs)。并对AF与CRC交集的DEGs进行功能富集分析，进一步通过构建蛋白质相互作用(protein-protein interaction, PPI)网络获得与两种疾病相关的关键基因并进行预后分析。结果 从GSE14975和GSE83889数据集分别识别了558和1 618个DEGs,其中有22个共享DEGs。基因本体论(Gene Ontology, GO)富集分析显示，差异基因参与的生物过程包括钙离子传输和T细胞受体信号传导。基于京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes, KEGG)的通路富集分析表明，差异基因显著富集于细胞因子-细胞因子受体相互作用等信号通路。PPI网络分析确定了14个蛋白节点和13条边，使用Cytohubba确定了6个关键基因。其中C-X-C基序趋化因子配体1(C-X-C motif chemokine ligand 1,CXCL1)和前血小板碱性蛋白(pro-platelet basic protein, PPBP)与多种疾病显著相关，并在CRC中表达上调。受试者工作特征曲线(receiver operating characteristic curve, ROC曲线)分析显示，CXCL1的诊断效率较高，曲线下面积(area under the curve, AUC)>90%。生存分析表明，CXCL1与CRC的预后相关。结论 本研究确定了与AF和CRC相关的关键基因，其中CXCL1可作为AF与CRC共病的潜在生物标志物，其调控的炎症通路或可成为跨疾病治疗靶点。更多还原

【Abstract】 Objective To analyze hub genes associated with atrial fibrillation(AF) and colorectal cancer(CRC) through gene expression data analysis. Methods Data were collected from GSE14975 and GSE83889 from the Gene Expression Omnibus(GEO) database. Differentially expressed genes(DEGs) with statistical parameters P<0.05 and∣fold change(FC)∣>1 were screened using Limma package. Functional enrichment analysis was performed on the DEGs at the intersection of AF and CRC, a protein-protein interaction(PPI) network was constructed to identify hub genes related to both diseases, followed by prognostic evaluation. Results A total of 558 and 1 618 DEGs were identified from GSE14975 and GSE83889, respectively, with 22 shared DEGs. Gene Ontology(GO) enrichment analysis showed involvement in processes such as calcium ion transport and T-cell receptor signaling. KEGG pathway enrichment analysis showed that the DEGs were significantly enriched in signaling pathways such as cytokine-cytokine receptor interaction. PPI network analysis identified 14 protein nodes and 13 edges, with 6 hub genes determined by Cytohubba. C-X-C motif chemokine ligand 1(CXCL1) and pro-platelet basic protein(PPBP) were significantly associated with multiple diseases and showed upregulated expression in CRC. Receiver operating characteristic(ROC) curve analysis showed high diagnostic efficiency for CXCL1(area under the curve, AUC)>90%. Survival analysis showed that CXCL1 was correlated with CRC prognosis. Conclusion The key genes associated with both AF and CRC were identified. CXCL1 may serve as a potential biomarker for AF-CRC comorbidity, and its modulation of inflammatory pathways could provide a therapeutic target across both diseases.更多还原