■角化已成为各种疾病进展的重要因素。本研究旨在评估角化相关基因(CRGs)对肝脏缺血再灌注损伤(HIRI)发展的潜在影响。
与HIRI相关的数据集来源于基因表达综合数据库。在HIRI和正常肝脏样品之间进行了涉及CRG的差异基因表达的比较分析。相关分析,功能富集分析,和蛋白质-蛋白质相互作用被用来理解这些基因的相互作用和作用。机器学习技术用于识别集线器基因。此外,分析了HIRI患者和对照组之间免疫细胞浸润的差异。使用定量实时PCR和蛋白质印迹来验证hub基因的表达。
■来自三个数据库的75个HIRI和80个对照样品被包括在生物信息学分析中。使用三种机器学习模型确定了三个中心CRG(NLRP3、ATP7B和NFE2L2)。使用hub基因的受试者工作特征(ROC)曲线评估诊断准确性,其产生0.832的ROC曲线下面积(AUC)。值得注意的是,在验证数据集GSE15480和GSE228782中,三个hub基因的AUC达到0.904.其他分析,包括列线图,决策曲线,和校准曲线,支持他们的诊断预测能力。富集分析表明这些基因参与与HIRI进展相关的多种途径。使用CIBERSORT和基因集富集分析的比较评估表明,这些hub基因在活化的树突状细胞中的表达升高,中性粒细胞,激活的CD4记忆T细胞,和HIRI样品中激活的肥大细胞与对照。ceRNA网络强调了基因之间复杂的调节相互作用。基因mRNA和蛋白质水平也在受HIRI影响的小鼠肝脏组织中得到证实。
■我们的发现提供了一个全面的了解角化和HIRI之间的关联,建立有希望的诊断模式并确定HIRI治疗的潜在治疗靶标。此外,我们的研究为深入研究HIRI的潜在机制提供了新的见解.
UNASSIGNED: Cuproptosis has emerged as a significant contributor in the progression of various diseases. This study aimed to assess the potential impact of cuproptosis-related genes (CRGs) on the development of hepatic ischemia and reperfusion injury (HIRI).
UNASSIGNED: The datasets related to HIRI were sourced from the Gene Expression Omnibus database. The comparative analysis of differential gene expression involving CRGs was performed between HIRI and normal liver samples. Correlation analysis, function enrichment analyses, and protein-protein interactions were employed to understand the interactions and roles of these genes. Machine learning techniques were used to identify hub genes. Additionally, differences in immune cell infiltration between HIRI patients and controls were analyzed. Quantitative real-time PCR and western blotting were used to verify the expression of the hub genes.
UNASSIGNED: Seventy-five HIRI and 80 control samples from three databases were included in the bioinformatics analysis. Three hub CRGs (NLRP3, ATP7B and NFE2L2) were identified using three machine learning models. Diagnostic accuracy was assessed using a receiver operating characteristic (ROC) curve for the hub genes, which yielded an area under the ROC curve (AUC) of 0.832. Remarkably, in the validation datasets GSE15480 and GSE228782, the three hub genes had AUC reached 0.904. Additional analyses, including nomograms, decision curves, and calibration curves, supported their predictive power for diagnosis. Enrichment analyses indicated the involvement of these genes in multiple pathways associated with HIRI progression. Comparative assessments using CIBERSORT and gene set enrichment analysis suggested elevated expression of these hub genes in activated dendritic cells, neutrophils, activated CD4 memory T cells, and activated mast cells in HIRI samples versus controls. A ceRNA network underscored a complex regulatory interplay among genes. The genes mRNA and protein levels were also verified in HIRI-affected mouse liver tissues.
UNASSIGNED: Our findings have provided a comprehensive understanding of the association between cuproptosis and HIRI, establishing a promising diagnostic pattern and identifying latent therapeutic targets for HIRI treatment. Additionally, our study offers novel insights to delve deeper into the underlying mechanisms of HIRI.