背景：原发性胆汁性胆管炎（PBC）是一种慢性自身免疫性肝病，如果没有适当治疗，最终会发展为肝硬化和肝细胞癌（HCC）。然而，PBC发病的基因表达及分子机制还没有被完全阐明。方法：从Gene Expression Omnibus（GEO）数据库下载了微阵列表达谱数据集GSE61260。使用R中的limma软件包，标准化数据以筛查差异表达基因（DEGs）。此外，进行了基因本体学（GO）和Kyoto Encyclopedia of Genes and Genomes（KEGG）通路富集分析。建立了蛋白质-蛋白质相互作用（PPI）网络以确定枢纽基因，并建立了一个转录因子-DEG-微RNA的综合调控网络。使用基因集富集分析（GSEA）分析了不同AKR1B10表达水平组的生物状态差异。进行了免疫组织化学（IHC）分析，以验证PBC患者肝脏中AKR1B10的表达。使用单因素方差分析（ANOVA）和Pearson相关分析评估了肝脏AKR1B10水平与临床参数的关联性。结果：本研究鉴定了22个上调和12个下调DEGs，这些DEGs在PBC患者和健康对照组之间存在差异。GO和KEGG分析表明，DEGs主要富集在免疫反应中。AKR1B10被确定为关键基因，并通过筛选PPI网络中的枢纽基因进一步分析。GSEA分析表明，AKR1B10的高表达可能促进PBC发展为HCC。免疫组织化学结果验证了PBC患者肝脏AKR1B10的表达增加，并显示其与PBC的严重程度呈正相关。结论：整合生物信息学分析和临床验证鉴定了AKR1B10作为PBC的枢纽基因。PBC患者AKR1B10表达的增加与疾病的严重程度有关，可能促进PBC向HCC的发展。版权所有2023 Wang、Zhang、Liu、Jiang、Fu和Peng。

Background: Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease that eventually progresses to cirrhosis and hepatocellular carcinoma (HCC) in the absence of proper treatment. However, Gene expression and molecular mechanisms involved in the pathogenesis of PBC have not been completely elucidated. Methods: Microarray expression profiling dataset GSE61260 was downloaded from the Gene Expression Omnibus (GEO) database. Data were normalized to screen differentially expressed genes (DEGs) using the limma package in R. Moreover, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed. A protein-protein interaction (PPI) network was constructed to identify hub genes and an integrative regulatory network of transcriptional factor-DEG-microRNA was established. Gene Set Enrichment Analysis (GSEA) was used to analyze differences in biological states for groups with different expressions of aldo-keto reductase family 1 member B10 (AKR1B10). Immunohistochemistry (IHC) analysis was performed to validate the expression of hepatic AKR1B10 in patients with PBC. The association of hepatic AKR1B10 levels with clinical parameters was evaluated using one-way analysis of variance (ANOVA) and Pearson's correlation analysis. Results: This study identified 22 upregulated and 12 downregulated DEGs between patients with PBC and healthy controls. GO and KEGG analysis revealed that DEGs were mainly enriched in immune reactions. AKR1B10 was identified as a key gene and was further analyzed by screening out hub genes from the PPI network. GSEA analysis indicated that high expression of AKR1B10 might promote PBC to develop into HCC. Immunohistochemistry results verified the increased expression of hepatic AKR1B10 in patients with PBC and demonstrated its positive correlation with the severity of PBC. Conclusion: AKR1B10 was identified as a hub gene in PBC by integrated bioinformatics analysis and clinical validation. The increase of AKR1B10 expression in patients with PBC was associated with disease severity and might promote the progression of PBC to HCC.Copyright © 2023 Wang, Zhang, Liu, Jiang, Fu and Peng.