Department of Critical Care Medicine, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, No.-1-1, Zhongfu Road, Nanjing, 210003, China.
Sci Rep. 2023 Feb 1;13(1):1876. doi: 10.1038/s41598-022-26794-8.
Cirrhosis is the most common subclass of liver disease worldwide and correlated to immune infiltration. However, the immune-related molecular mechanism underlying cirrhosis remains obscure. Two gene expression profiles GSE89377 and GSE139602 were investigated to identify differentially expressed genes (DEGs) related to cirrhosis. Enrichment analysis for DEGs was conducted. Next, the immune infiltration of DEGs was evaluated using CIBERSORT algorithm. The hub DEGs with tight connectivity were identified using the String and Cytoscape databases, and the expression difference of these hub genes between normal liver and cirrhosis samples was determined. Moreover, in order to evaluate the discriminatory ability of hub genes and obtained the area under the receiver operating characteristic curve values in the GSE89377 and GSE139602 datasets. Finally, the association between hub DEGs and immune cell infiltration was explored by Spearman method. Among the 299 DEGs attained, 136 were up-regulated and 163 were down-regulated. Then the enrichment function analysis of DEGs and CIBERSORT algorithm showed significant enrichment in immune and inflammatory responses. And four hub DEGs (ACTB, TAGLN, VIM, SOX9) were identified, which also showed a diagnostic value in the GSE89377 and GSE 139,602 datasets. Finally, the immune infiltration analysis indicated that, these hub DEGs were highly related to immune cells. This study revealed key DEGs involved in inflammatory immune responses of cirrhosis, which could be used as biomarkers for diagnosis or therapeutic targets of cirrhosis.
肝硬化是全球最常见的肝病亚类,与免疫浸润相关。然而,肝硬化的免疫相关分子机制仍不清楚。本研究分别分析了 GSE89377 和 GSE139602 两个基因表达谱,以鉴定与肝硬化相关的差异表达基因(DEGs)。对 DEGs 进行富集分析。接下来,使用 CIBERSORT 算法评估 DEGs 的免疫浸润。使用 String 和 Cytoscape 数据库鉴定具有紧密连接的枢纽 DEGs,并确定这些枢纽基因在正常肝组织和肝硬化样本之间的表达差异。此外,为了评估枢纽基因的区分能力,在 GSE89377 和 GSE139602 数据集上计算了获得的接收器操作特征曲线下面积值。最后,通过 Spearman 方法探讨了枢纽 DEGs 与免疫细胞浸润之间的相关性。在获得的 299 个 DEGs 中,有 136 个上调,163 个下调。然后,DEGs 的富集功能分析和 CIBERSORT 算法显示,免疫和炎症反应存在明显富集。确定了 4 个枢纽 DEGs(ACTB、TAGLN、VIM、SOX9),它们在 GSE89377 和 GSE139602 数据集也具有诊断价值。最后,免疫浸润分析表明,这些枢纽 DEGs 与免疫细胞高度相关。本研究揭示了参与肝硬化炎症免疫反应的关键 DEGs,它们可作为肝硬化诊断的生物标志物或治疗靶点。