筛选慢性阻塞性肺疾病(chronic obstructive pulmonary disease, COPD)和心肌梗死(myocardial infarction)生物标志物，探讨潜在共同治疗靶点。

基于GEO数据集与R语言确定COPD和心肌梗死共同差异表达基因(differentially expressed genes, DEGs)。对DEGs进行基因本体/京都基因和基因组百科(Gene ontology/Kyoto encyclopedia of genes and genome, GO/KEGG)通路富集分析。利用STRING数据库构建蛋白质互作网络(protein-protein interaction, PPI)，结合加权基因共表达网络分析(weighted correlation network analysis, WGCNA)筛选关键基因。使用外部数据集验证关键基因表达。应用CIBERSORT算法对心肌梗死数据集进行免疫浸润分析，判断关键基因与免疫细胞浸润水平的相关性。构建转录因子(transcription factor, TF)-miRNA共调控网络。预测对COPD并发心肌梗死具有潜在治疗作用的候选药物分子。

基于GEO数据库，对COPD及心肌梗死数据集进行差异表达分析，获得49个DEGs。GO分析显示，上调基因主要富集于细胞因子正向调控、模式识别受体活性功能。下调基因富集于白细胞介导的细胞毒性功能。KEGG分析表明，上调基因富集于NF-κB信号通路，下调基因未见显著富集通路。通过PPI网络及WGCNA分析，筛选出6个DEGs，经外部数据集验证，筛选出3个DEGs(TLR8、IL1B及S100A12)。通过受试者工作曲线(receiver operating characteristic, ROC)得出RTLR8和IL1B与香烟烟雾暴露及COPD合并心梗患者复发相关。CIBERSORT分析显示心肌梗死样本与13种免疫细胞浸润存在显著差异。单基因集富集分析(single sample gene set enrichment analysis, ssGSEA)表明关键基因与静息记忆CD4^＋ T细胞呈负相关，与单核细胞、活化肥大细胞及中性粒细胞呈正相关。TF-miRNA网络提示两种疾病的共同致病通路可能为E2F1-miR-9-TLR8。3个关键DEGs药物分子预测提示米格列醇、四(2-吡啶甲基)乙二胺、环己酰亚胺等可能对两种疾病具有共同治疗潜力。

TLR8，IL1B及S100A12是COPD并发心肌梗死潜在生物标志物和治疗靶点。香烟烟雾通过影响TLR8/IL1B通路增加心肌梗死复发风险。中性粒细胞介导免疫反应是病理特征。米格列醇、四(2-吡啶甲基)乙二胺、环己酰亚胺可能对COPD并发心肌梗死具有治疗意义。

To screen for biomarkers of chronic obstructive pulmonary disease (COPD) and myocardial infarction (MI) and explore potential common therapeutic targets.

Common differentially expressed genes (DEGs) of COPD and MI were identified based on GEO datasets and R language. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the DEGs. A protein-protein interaction (PPI) network was constructed using the STRING database, and key genes were screened in combination with weighted correlation network analysis (WGCNA). Expression of key genes was validated using external datasets. Immune infiltration analysis of MI datasets was conducted using the CIBERSORT algorithm to assess the correlation between key genes and immune cell infiltration levels. A transcription factor (TF)-miRNA coregulatory network was constructed. Candidate drug molecules with potential therapeutic effects on COPD-MI comorbidity were predicted.

Differential expression analysis of COPD and MI datasets based on the GEO database identified 49 DEGs. GO analysis showed that upregulated genes were mainly enriched in positive regulation of cytokines and pattern recognition receptor activity, while downregulated genes were enriched in leukocytemediated cytotoxicity. KEGG analysis revealed that upregulated genes were significantly enriched in the NF-κB signaling pathway, whereas no significant enrichment pathway was found for downregulated genes. Through PPI network and WGCNA analyses, six DEGs were selected. After validation with external datasets, three DEGs (TLR8, IL1B, and S100A12) were ultimately identified. Receiver operating characteristic (ROC) curves indicated that TLR8 and IL1B were associated with cigarette smoke exposure and recurrence of COPD complicated with MI. CIBERSORT analysis showed significant differences in the infiltration of 13 immune cell types between MI samples and controls. Singlesample Gene Set Enrichment Analysis (ssGSEA) revealed that key genes were negatively correlated with resting memory CD4⁺ T cells and positively correlated with monocytes, activated mast cells, and neutrophils. The TFmiRNA network suggested that the E2F1miR9TLR8 axis may be a common pathogenic pathway for the two diseases. Drug molecule prediction for the three key DEGs indicated that miglitol, TPEN and cycloheximide may have potential as common therapeutic agents for both diseases.

TLR8, IL1B and S100A12 may be therapeutic targets for COPD and MI. TLR8, IL1B serve as potential biomarkers and therapeutic targets for COPD-MI comorbidity. Cigarette smoke exposure may increase MI recurrence risk by affecting the TLR8/IL1B pathway. Neutrophil-mediated immune responses represent a crucial pathological feature shared by both diseases. Candidate drugs provide new research directions for comorbidity treatment. Miglitol, TPEN and cycloheximide may have potential therapeutic effects on both diseases.