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.

中文翻译：

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通过综合生物信息学分析和实验验证将 AKR1B10 鉴定为原发性胆汁性胆管炎的关键基因

背景：原发性胆汁性胆管炎 (PBC) 是一种慢性自身免疫性肝病，在没有适当治疗的情况下最终会发展为肝硬化和肝细胞癌 (HCC)。然而，参与 PBC 发病机制的基因表达和分子机制尚未完全阐明。方法：微阵列表达谱数据集 GSE61260 从 Gene Expression Omnibus (GEO) 数据库下载。使用 R 中的 limma 包对数据进行标准化以筛选差异表达基因 (DEG)。此外，还进行了基因本体论 (GO) 和京都基因百科全书和基因组通路 (KEGG) 富集分析。构建了蛋白质-蛋白质相互作用 (PPI) 网络以识别中枢基因，并建立了转录因子-DEG-microRNA 的整合调控网络。基因集富集分析 (GSEA) 用于分析醛酮还原酶家族 1 成员 B10 (AKR1B10) 不同表达组的生物状态差异。进行免疫组织化学 (IHC) 分析以验证 PBC 患者肝脏 AKR1B10 的表达。使用单因素方差分析 (ANOVA) 和 Pearson 相关分析评估肝脏 AKR1B10 水平与临床参数的关联。结果：本研究在 PBC 患者和健康对照之间确定了 22 个上调和 12 个下调的 DEG。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，并通过从 PPI 网络中筛选出枢纽基因进行进一步分析。GSEA分析表明AKR1B10的高表达可能促进PBC发展为HCC。免疫组织化学结果证实PBC患者肝脏AKR1B10表达增加，并证明其与PBC严重程度呈正相关。PBC 患者 AKR1B10 表达的增加与疾病严重程度相关，并可能促进 PBC 向 HCC 的进展。