Department of Geriatric Cardiology, General Hospital of Southern Theater Command; Guangzhou Key Laboratory of Cardiac Rehabilitation; Branch of National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital.
Department of Geriatric Cardiology, General Hospital of Southern Theater Command; The First School of Clinical Medicine, Southern Medical University.
J Vis Exp. 2024 Aug 30(210). doi: 10.3791/67328.
Non-alcoholic fatty liver disease (NAFLD) and myocardial infarction (MI) are two major health burdens with significant prevalence and mortality. This study aimed to explore the co-expressed genes to understand the relationship between NAFLD and MI and identify potential crucial biomarkers of NAFLD-related MI using bioinformatics and machine learning. Functional enrichment analysis was conducted, a co-protein-protein interaction (PPI) network diagram was constructed, and support vector machine-recursive feature elimination (SVM-RFE) and least absolute shrinkage and selection operator (LASSO) techniques were employed to identify one differentially expressed gene (DEG), Thrombospondin 1 (THBS1). THBS1 demonstrated strong performance in distinguishing NAFLD patients (AUC = 0.981) and MI patients (AUC = 0.900). Immuno-infiltration analysis revealed significantly lower CD8+ T cells and higher neutrophil levels in patients with NAFLD and MI. CD8+ T cells and neutrophils were effective in distinguishing NAFLD/MI from healthy controls. Correlation analysis showed that THBS1 was positively correlated with CCR (chemokine receptor), MHC class (major histocompatibility complex class), neutrophils, parainflammation, and Tfh (follicular helper T cells), and negatively correlated with CD8+ T cells, cytolytic activity, and TIL (tumor-infiltrating lymphocytes) in NAFLD and MI patients. THBS1 emerged as a novel biomarker for diagnosing NAFLD/MI in comparison to healthy controls. The results indicate that CD8+ T cells and neutrophils could serve as inflammatory immune features for differentiating patients with NAFLD/MI from healthy individuals.
非酒精性脂肪性肝病(NAFLD)和心肌梗死(MI)是两种主要的健康负担,具有显著的患病率和死亡率。本研究旨在通过生物信息学和机器学习探索共表达基因,以了解 NAFLD 与 MI 之间的关系,并鉴定与 NAFLD 相关的 MI 的潜在关键生物标志物。进行了功能富集分析,构建了共蛋白-蛋白相互作用(PPI)网络图,并采用支持向量机-递归特征消除(SVM-RFE)和最小绝对收缩和选择算子(LASSO)技术鉴定一个差异表达基因(DEG),即血小板反应蛋白 1(THBS1)。THBS1 在区分 NAFLD 患者(AUC=0.981)和 MI 患者(AUC=0.900)方面表现出很强的性能。免疫浸润分析显示,NAFLD 和 MI 患者的 CD8+T 细胞和中性粒细胞水平明显较低。CD8+T 细胞和中性粒细胞有效地区分了 NAFLD/MI 与健康对照组。相关性分析表明,THBS1 与 NAFLD 和 MI 患者中的趋化因子受体(CCR)、主要组织相容性复合体(MHC)类、中性粒细胞、副炎症和滤泡辅助 T 细胞(Tfh)呈正相关,与 CD8+T 细胞、细胞溶解活性和肿瘤浸润淋巴细胞(TIL)呈负相关。THBS1 作为一种新的生物标志物,与健康对照组相比,可用于诊断 NAFLD/MI。结果表明,CD8+T 细胞和中性粒细胞可作为区分 NAFLD/MI 患者与健康个体的炎症免疫特征。