Chen Qiu, Zhang Ji-Lei, Yang Jie-Shun, Jin Qing, Yang Jun, Xue Qiang, Guang Xue-Feng
Department of Cardiology, Yan'an Hospital Affiliated to Kunming Medical University, Kunming, People's Republic of China.
Department of Pathology, The Second Affiliated Hospital of Kunming Medical University, Kunming, People's Republic of China.
J Inflamm Res. 2024 Jul 10;17:4525-4548. doi: 10.2147/JIR.S457469. eCollection 2024.
Necroptosis, a monitored form of inflammatory cell death, contributes to coronary heart disease (CHD) progression. This study examined the potential of using necroptosis genes as diagnostic markers for CHD and sought to elucidate the underlying roles.
Through bioinformatic analysis of GSE20680 and GSE20681, we first identified the differentially expressed genes (DEGs) related to necroptosis in CHD. Hub genes were identified using least absolute shrinkage and selection operator (LASSO) regression and random forest analysis after studying immune infiltration and transcription factor-miRNA interaction networks according to the DEGs. Quantitative polymerase chain reaction and immunohistochemistry were used to further investigate hub gene expression in vivo, for which a diagnostic model was constructed and the predictive efficacy was validated. Finally, the CHD group was categorized into high- and low-score groups in accordance with the single-sample gene set enrichment analysis (ssGSEA) score of the necroptosis genes. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, GSEA, and further immune infiltration analyses were performed on the two groups to explore the possible roles of hub genes.
Based on the results of the LASSO regression and random forest analyses, four genes were used to construct a diagnostic model to establish a nomogram. Additionally, an extensive analysis of all seventeen necroptosis genes revealed notable distinctions in expression between high-risk and low-risk groups. Evaluation of immune infiltration revealed that neutrophils, monocytes, B cells, and activated dendritic cells were highly distributed in the peripheral blood of patients with CHD. Specifically, the high CHD score group exhibited greater neutrophil and monocyte infiltration. Conversely, the high-score group showed lower infiltration of M0 and M2 macrophages, CD8+ T, plasma, and resting mast cells.
, and may be prospective biomarkers for CHD diagnosis. These findings offer plausible explanations for the role of necroptosis in CHD progression through immune infiltration and inflammatory response.
坏死性凋亡是一种受调控的炎症性细胞死亡形式，促进冠心病（CHD）进展。本研究检测了将坏死性凋亡基因用作CHD诊断标志物的潜力，并试图阐明其潜在作用。
通过对GSE20680和GSE20681进行生物信息学分析，我们首先鉴定出CHD中与坏死性凋亡相关的差异表达基因（DEGs）。在根据DEGs研究免疫浸润和转录因子- miRNA相互作用网络后，使用最小绝对收缩和选择算子（LASSO）回归及随机森林分析鉴定枢纽基因。采用定量聚合酶链反应和免疫组织化学进一步研究枢纽基因在体内的表达，构建诊断模型并验证其预测效能。最后，根据坏死性凋亡基因的单样本基因集富集分析（ssGSEA）评分将CHD组分为高分和低分两组。对两组进行基因本体论、京都基因与基因组百科全书、基因集富集分析（GSEA）以及进一步的免疫浸润分析，以探索枢纽基因的可能作用。
基于LASSO回归和随机森林分析结果，使用四个基因构建诊断模型并建立列线图。此外，对所有17个坏死性凋亡基因的广泛分析显示，高风险和低风险组之间在表达上存在显著差异。免疫浸润评估显示，中性粒细胞、单核细胞、B细胞和活化树突状细胞在CHD患者外周血中高度分布。具体而言，CHD高分患者组中性粒细胞和单核细胞浸润更明显。相反，高分患者组M0和M2巨噬细胞、CD8 + T细胞、浆细胞和静息肥大细胞浸润较少。
以及 可能是CHD诊断的潜在生物标志物。这些发现为坏死性凋亡通过免疫浸润和炎症反应在CHD进展中的作用提供了合理的解释。
