Identification of AKR1B10 as a key gene in primary biliary cholangitis by integrated bioinformatics analysis and experimental validation
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 compl...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2023.1124956/full |
| _version_ | 1811168402223398912 |
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| author | Huiwen Wang Jian Zhang Jinqing Liu Yongfang Jiang Lei Fu Shifang Peng |
| author_facet | Huiwen Wang Jian Zhang Jinqing Liu Yongfang Jiang Lei Fu Shifang Peng |
| author_sort | Huiwen Wang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-10T16:25:41Z |
| format | Article |
| id | doaj.art-51717564770342c2a591df856837a905 |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-04-10T16:25:41Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-51717564770342c2a591df856837a9052023-02-09T05:38:51ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2023-02-011010.3389/fmolb.2023.11249561124956Identification of AKR1B10 as a key gene in primary biliary cholangitis by integrated bioinformatics analysis and experimental validationHuiwen Wang0Jian Zhang1Jinqing Liu2Yongfang Jiang3Lei Fu4Shifang Peng5Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Infectious Diseases, Second Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, ChinaBackground: 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.https://www.frontiersin.org/articles/10.3389/fmolb.2023.1124956/fullAKR1B10primary biliary cholangitisintegrated bioinformaticsdifferentially expressed geneshub genes |
| spellingShingle | Huiwen Wang Jian Zhang Jinqing Liu Yongfang Jiang Lei Fu Shifang Peng Identification of AKR1B10 as a key gene in primary biliary cholangitis by integrated bioinformatics analysis and experimental validation Frontiers in Molecular Biosciences AKR1B10 primary biliary cholangitis integrated bioinformatics differentially expressed genes hub genes |
| title | Identification of AKR1B10 as a key gene in primary biliary cholangitis by integrated bioinformatics analysis and experimental validation |
| title_full | Identification of AKR1B10 as a key gene in primary biliary cholangitis by integrated bioinformatics analysis and experimental validation |
| title_fullStr | Identification of AKR1B10 as a key gene in primary biliary cholangitis by integrated bioinformatics analysis and experimental validation |
| title_full_unstemmed | Identification of AKR1B10 as a key gene in primary biliary cholangitis by integrated bioinformatics analysis and experimental validation |
| title_short | Identification of AKR1B10 as a key gene in primary biliary cholangitis by integrated bioinformatics analysis and experimental validation |
| title_sort | identification of akr1b10 as a key gene in primary biliary cholangitis by integrated bioinformatics analysis and experimental validation |
| topic | AKR1B10 primary biliary cholangitis integrated bioinformatics differentially expressed genes hub genes |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2023.1124956/full |
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