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Differences of core genes in liver fibrosis and hepatocellular carcinoma: Evidence from integrated bioinformatics and immunohistochemical analysis
BACKGROUND: Liver fibrosis and hepatocellular carcinoma (HCC) are common adverse consequences of chronic liver injury. The interaction of various risk factors may cause them to happen. Identification of specific biomarkers is of great significance for understanding the occurrence, development mechan...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Baishideng Publishing Group Inc
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9305567/ https://www.ncbi.nlm.nih.gov/pubmed/36051101 http://dx.doi.org/10.4251/wjgo.v14.i7.1265 |
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author | Li, Yue Yuan, Shou-Li Yin, Jing-Ya Yang, Kun Zhou, Xin-Gang Xie, Wen Wang, Qi |
author_facet | Li, Yue Yuan, Shou-Li Yin, Jing-Ya Yang, Kun Zhou, Xin-Gang Xie, Wen Wang, Qi |
author_sort | Li, Yue |
collection | PubMed |
description | BACKGROUND: Liver fibrosis and hepatocellular carcinoma (HCC) are common adverse consequences of chronic liver injury. The interaction of various risk factors may cause them to happen. Identification of specific biomarkers is of great significance for understanding the occurrence, development mechanisms, and determining the novel tools for diagnosis and treatment of both liver fibrosis and HCC. AIM: To identify liver fibrosis-related core genes, we analyzed the differential expression pattern of core genes in liver fibrosis and HCC. METHODS: Gene expression profiles of three datasets, GSE14323, GSE36411, and GSE89377, obtained from the Gene Expression Omnibus (GEO) database, were analyzed, and differentially expressed genes (DEGs) between patients with liver cirrhosis and healthy controls were identified by screening via R software packages and online tool for Venn diagrams. The WebGestalt online tool was used to identify DEGs enriched in biological processes, molecular functions, cellular components, and Kyoto Encyclopedia of Genes and Genomes pathways. The protein–protein interactions of DEGs were visualized using Cytoscape with STRING. Next, the expression pattern of core genes was analyzed using Western blot and immunohistochemistry in a carbon tetrachloride (CCl(4))-induced liver cirrhosis mouse model and in patient liver samples. Finally, Kaplan-Meier curves were constructed using the Kaplan-Meier plotter online server. RESULTS: Forty-five DEGs (43 upregulated and 2 downregulated genes) associated with liver cirrhosis were identified from three GEO datasets. Ten hub genes were identified, which were upregulated in liver cirrhosis. Western blot and immunohistochemical analyses of the three core genes, decorin (DCN), dermatopontin (DPT), and SRY-box transcription factor 9 (SOX9), revealed that they were highly expressed in the CCl(4)-induced liver cirrhosis mouse model. The expression levels of DCN and SOX 9 were positively correlated with the degree of fibrosis, and SOX 9 level in HCC patients was significantly higher than that in fibrosis patients. However, high expression of DPT was observed only in patients with liver fibrosis, and its expression in HCC was low. The gene expression profiling interactive analysis server (GEPIA) showed that SOX9 was significantly upregulated whereas DCN and DPT were significantly downregulated in patients with HCC. In addition, the Kaplan-Meier curves showed that HCC patients with higher SOX9 expression had significantly lower 5-year survival rate, while patients with higher expression of DCN or DPT had significantly higher 5-year survival rates. CONCLUSION: The expression levels of DCN, DPT, and SOX9 were positively correlated with the degree of liver fibrosis but showed different correlations with the 5-year survival rates of HCC patients. |
format | Online Article Text |
id | pubmed-9305567 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Baishideng Publishing Group Inc |
record_format | MEDLINE/PubMed |
spelling | pubmed-93055672022-08-31 Differences of core genes in liver fibrosis and hepatocellular carcinoma: Evidence from integrated bioinformatics and immunohistochemical analysis Li, Yue Yuan, Shou-Li Yin, Jing-Ya Yang, Kun Zhou, Xin-Gang Xie, Wen Wang, Qi World J Gastrointest Oncol Clinical and Translational Research BACKGROUND: Liver fibrosis and hepatocellular carcinoma (HCC) are common adverse consequences of chronic liver injury. The interaction of various risk factors may cause them to happen. Identification of specific biomarkers is of great significance for understanding the occurrence, development mechanisms, and determining the novel tools for diagnosis and treatment of both liver fibrosis and HCC. AIM: To identify liver fibrosis-related core genes, we analyzed the differential expression pattern of core genes in liver fibrosis and HCC. METHODS: Gene expression profiles of three datasets, GSE14323, GSE36411, and GSE89377, obtained from the Gene Expression Omnibus (GEO) database, were analyzed, and differentially expressed genes (DEGs) between patients with liver cirrhosis and healthy controls were identified by screening via R software packages and online tool for Venn diagrams. The WebGestalt online tool was used to identify DEGs enriched in biological processes, molecular functions, cellular components, and Kyoto Encyclopedia of Genes and Genomes pathways. The protein–protein interactions of DEGs were visualized using Cytoscape with STRING. Next, the expression pattern of core genes was analyzed using Western blot and immunohistochemistry in a carbon tetrachloride (CCl(4))-induced liver cirrhosis mouse model and in patient liver samples. Finally, Kaplan-Meier curves were constructed using the Kaplan-Meier plotter online server. RESULTS: Forty-five DEGs (43 upregulated and 2 downregulated genes) associated with liver cirrhosis were identified from three GEO datasets. Ten hub genes were identified, which were upregulated in liver cirrhosis. Western blot and immunohistochemical analyses of the three core genes, decorin (DCN), dermatopontin (DPT), and SRY-box transcription factor 9 (SOX9), revealed that they were highly expressed in the CCl(4)-induced liver cirrhosis mouse model. The expression levels of DCN and SOX 9 were positively correlated with the degree of fibrosis, and SOX 9 level in HCC patients was significantly higher than that in fibrosis patients. However, high expression of DPT was observed only in patients with liver fibrosis, and its expression in HCC was low. The gene expression profiling interactive analysis server (GEPIA) showed that SOX9 was significantly upregulated whereas DCN and DPT were significantly downregulated in patients with HCC. In addition, the Kaplan-Meier curves showed that HCC patients with higher SOX9 expression had significantly lower 5-year survival rate, while patients with higher expression of DCN or DPT had significantly higher 5-year survival rates. CONCLUSION: The expression levels of DCN, DPT, and SOX9 were positively correlated with the degree of liver fibrosis but showed different correlations with the 5-year survival rates of HCC patients. Baishideng Publishing Group Inc 2022-07-15 2022-07-15 /pmc/articles/PMC9305567/ /pubmed/36051101 http://dx.doi.org/10.4251/wjgo.v14.i7.1265 Text en ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved. https://creativecommons.org/licenses/by-nc/4.0/This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/ |
spellingShingle | Clinical and Translational Research Li, Yue Yuan, Shou-Li Yin, Jing-Ya Yang, Kun Zhou, Xin-Gang Xie, Wen Wang, Qi Differences of core genes in liver fibrosis and hepatocellular carcinoma: Evidence from integrated bioinformatics and immunohistochemical analysis |
title | Differences of core genes in liver fibrosis and hepatocellular carcinoma: Evidence from integrated bioinformatics and immunohistochemical analysis |
title_full | Differences of core genes in liver fibrosis and hepatocellular carcinoma: Evidence from integrated bioinformatics and immunohistochemical analysis |
title_fullStr | Differences of core genes in liver fibrosis and hepatocellular carcinoma: Evidence from integrated bioinformatics and immunohistochemical analysis |
title_full_unstemmed | Differences of core genes in liver fibrosis and hepatocellular carcinoma: Evidence from integrated bioinformatics and immunohistochemical analysis |
title_short | Differences of core genes in liver fibrosis and hepatocellular carcinoma: Evidence from integrated bioinformatics and immunohistochemical analysis |
title_sort | differences of core genes in liver fibrosis and hepatocellular carcinoma: evidence from integrated bioinformatics and immunohistochemical analysis |
topic | Clinical and Translational Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9305567/ https://www.ncbi.nlm.nih.gov/pubmed/36051101 http://dx.doi.org/10.4251/wjgo.v14.i7.1265 |
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