Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
Beijing University of Chinese Medicine, Beijing, China.
Hereditas. 2024 Oct 1;161(1):32. doi: 10.1186/s41065-024-00309-z.
The most common progressive form of non-alcoholic fatty liver disease (NAFLD) is non-alcoholic steatohepatitis (NASH), which is characterized by the development of cirrhosis, and requires liver transplantation. We screened for the differentially expressed necroptosis-related genes in NASH in this study, and analyzed immune infiltration through microarray and bioinformatics analysis to identify potential biomarkers, and explore the molecular mechanisms involved in NASH.
The GSE24807 microarray dataset of NASH patients and healthy controls was downloaded, and we identified the differentially expressed genes (DEGs). Necroptosis-related differential genes (NRDEGs) were extracted from these DEGs, and functionally annotated by enrichment analyses. The core genes were obtained by constructing gene co-expression networks using weighted gene co-expression network analysis (WGCNA). Finally, the transcription factor (TF) regulatory network and the mRNA-miRNA network were constructed, and the infiltrating immune cell populations were analyzed with CIBERSORT.
We identified six necroptosis-related genes (CASP1, GLUL, PYCARD, IL33, SHARPIN, and IRF9), and they are potential diagnostic biomarkers for NASH. In particular, PYCARD is a potential biomarker for NAFLD progression. Analyses of immune infiltration showed that M2 macrophages, γδ T cells, and T follicular helper cells were associated with the immune microenvironment of NASH, which is possibly regulated by CASP1, IL33, and IRF9.
We identified six necroptosis-related genes in NASH, which are also potential diagnostic biomarkers. Our study provides new insights into the molecular mechanisms and immune microenvironment of NASH.
非酒精性脂肪性肝病（NAFLD）最常见的进展形式是非酒精性脂肪性肝炎（NASH），其特征为肝硬化的发展，需要进行肝移植。本研究通过微阵列和生物信息学分析筛选 NASH 中差异表达的坏死性凋亡相关基因，分析免疫浸润，以识别潜在的生物标志物，并探讨 NASH 涉及的分子机制。
下载 NASH 患者和健康对照的 GSE24807 微阵列数据集，鉴定差异表达基因（DEGs）。从这些 DEGs 中提取坏死性凋亡相关差异基因（NRDEGs），并通过富集分析进行功能注释。使用加权基因共表达网络分析（WGCNA）构建基因共表达网络，获取核心基因。最后构建转录因子（TF）调控网络和 mRNA-miRNA 网络，并通过 CIBERSORT 分析浸润免疫细胞群。
我们鉴定了六个与坏死性凋亡相关的基因（CASP1、GLUL、PYCARD、IL33、SHARPIN 和 IRF9），它们可能是 NASH 的潜在诊断生物标志物。特别是 PYCARD 是 NAFLD 进展的潜在生物标志物。免疫浸润分析表明，M2 巨噬细胞、γδ T 细胞和滤泡辅助 T 细胞与 NASH 的免疫微环境相关，这可能受 CASP1、IL33 和 IRF9 的调控。
我们鉴定了 NASH 中的六个与坏死性凋亡相关的基因，它们也可能是潜在的诊断生物标志物。本研究为 NASH 的分子机制和免疫微环境提供了新的见解。
