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Identification and validation of three core genes in p53 signaling pathway in hepatitis B virus-related hepatocellular carcinoma
BACKGROUND: Hepatocellular carcinoma (HCC) is a common cancer and the leading cause is persistent hepatitis B virus (HBV) infection. We aimed to identify some core genes and pathways for HBV-related HCC. METHODS: Gene expression profiles of GSE62232, GSE121248, and GSE94660 were available from Gene...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938465/ https://www.ncbi.nlm.nih.gov/pubmed/33685467 http://dx.doi.org/10.1186/s12957-021-02174-w |
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author | Yu, Mingxue Xu, Wenli Jie, Yusheng Pang, Jiahui Huang, Siqi Cao, Jing Gong, Jiao Li, Xinhua Chong, Yutian |
author_facet | Yu, Mingxue Xu, Wenli Jie, Yusheng Pang, Jiahui Huang, Siqi Cao, Jing Gong, Jiao Li, Xinhua Chong, Yutian |
author_sort | Yu, Mingxue |
collection | PubMed |
description | BACKGROUND: Hepatocellular carcinoma (HCC) is a common cancer and the leading cause is persistent hepatitis B virus (HBV) infection. We aimed to identify some core genes and pathways for HBV-related HCC. METHODS: Gene expression profiles of GSE62232, GSE121248, and GSE94660 were available from Gene Expression Omnibus (GEO). The GSE62232 and GSE121248 profiles were the analysis datasets and GSE94660 was the validation dataset. The GEO2R online tool and Venn diagram software were applied to analyze commonly differentially expressed genes between HBV-related HCC tissues and normal tissues. Then, functional enrichment analysis using Gene Ontology (GO) and the Kyoto Encyclopedia of Gene and Genome (KEGG) as well as the protein-protein interaction (PPI) network was conducted. The overall survival rates and the expression levels were detected by Kaplan-Meier plotter and Gene Expression Profiling Interactive Analysis (GEPIA). Next, gene set enrichment analysis (GSEA) was performed to verify the KEGG pathway analysis. Furthermore, quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was performed to validate the levels of these three core genes in tumor tissues and adjacent non-tumor liver tissues from 12 HBV related HCC patients, HBV-associated liver cancer cell lines and normal liver cell lines, and HepG2 with p53 knockdown or deletion, respectively. RESULTS: Fifteen highly expressed genes associated with significantly worse prognoses were selected and CCNB1, CDK1, and RRM2 in the p53 signaling pathway were identified as core genes. GSEA results showed that samples highly expressing three core genes were all enriched in the p53 signaling pathway in a validation dataset (P < 0.0001). The expression of these three core genes in tumor tissue samples was higher than that in relevant adjacent non-tumor liver tissues (P < 0.0001). Furthermore, we also found that the above genes were highly expressed in liver cancer cell lines compared with normal liver cells. In addition, we found that the expression of these three core genes in p53 knockdown or knockout HCC cell lines was lower than that in negative control HCC cell lines (P < 0.05). CONCLUSIONS: CCNB1, CDK1, and RRM2 were enriched in the p53 signaling pathway and could be potential biomarkers and therapeutic targets for HBV-related HCC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12957-021-02174-w. |
format | Online Article Text |
id | pubmed-7938465 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-79384652021-03-09 Identification and validation of three core genes in p53 signaling pathway in hepatitis B virus-related hepatocellular carcinoma Yu, Mingxue Xu, Wenli Jie, Yusheng Pang, Jiahui Huang, Siqi Cao, Jing Gong, Jiao Li, Xinhua Chong, Yutian World J Surg Oncol Research BACKGROUND: Hepatocellular carcinoma (HCC) is a common cancer and the leading cause is persistent hepatitis B virus (HBV) infection. We aimed to identify some core genes and pathways for HBV-related HCC. METHODS: Gene expression profiles of GSE62232, GSE121248, and GSE94660 were available from Gene Expression Omnibus (GEO). The GSE62232 and GSE121248 profiles were the analysis datasets and GSE94660 was the validation dataset. The GEO2R online tool and Venn diagram software were applied to analyze commonly differentially expressed genes between HBV-related HCC tissues and normal tissues. Then, functional enrichment analysis using Gene Ontology (GO) and the Kyoto Encyclopedia of Gene and Genome (KEGG) as well as the protein-protein interaction (PPI) network was conducted. The overall survival rates and the expression levels were detected by Kaplan-Meier plotter and Gene Expression Profiling Interactive Analysis (GEPIA). Next, gene set enrichment analysis (GSEA) was performed to verify the KEGG pathway analysis. Furthermore, quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was performed to validate the levels of these three core genes in tumor tissues and adjacent non-tumor liver tissues from 12 HBV related HCC patients, HBV-associated liver cancer cell lines and normal liver cell lines, and HepG2 with p53 knockdown or deletion, respectively. RESULTS: Fifteen highly expressed genes associated with significantly worse prognoses were selected and CCNB1, CDK1, and RRM2 in the p53 signaling pathway were identified as core genes. GSEA results showed that samples highly expressing three core genes were all enriched in the p53 signaling pathway in a validation dataset (P < 0.0001). The expression of these three core genes in tumor tissue samples was higher than that in relevant adjacent non-tumor liver tissues (P < 0.0001). Furthermore, we also found that the above genes were highly expressed in liver cancer cell lines compared with normal liver cells. In addition, we found that the expression of these three core genes in p53 knockdown or knockout HCC cell lines was lower than that in negative control HCC cell lines (P < 0.05). CONCLUSIONS: CCNB1, CDK1, and RRM2 were enriched in the p53 signaling pathway and could be potential biomarkers and therapeutic targets for HBV-related HCC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12957-021-02174-w. BioMed Central 2021-03-08 /pmc/articles/PMC7938465/ /pubmed/33685467 http://dx.doi.org/10.1186/s12957-021-02174-w Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Yu, Mingxue Xu, Wenli Jie, Yusheng Pang, Jiahui Huang, Siqi Cao, Jing Gong, Jiao Li, Xinhua Chong, Yutian Identification and validation of three core genes in p53 signaling pathway in hepatitis B virus-related hepatocellular carcinoma |
title | Identification and validation of three core genes in p53 signaling pathway in hepatitis B virus-related hepatocellular carcinoma |
title_full | Identification and validation of three core genes in p53 signaling pathway in hepatitis B virus-related hepatocellular carcinoma |
title_fullStr | Identification and validation of three core genes in p53 signaling pathway in hepatitis B virus-related hepatocellular carcinoma |
title_full_unstemmed | Identification and validation of three core genes in p53 signaling pathway in hepatitis B virus-related hepatocellular carcinoma |
title_short | Identification and validation of three core genes in p53 signaling pathway in hepatitis B virus-related hepatocellular carcinoma |
title_sort | identification and validation of three core genes in p53 signaling pathway in hepatitis b virus-related hepatocellular carcinoma |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938465/ https://www.ncbi.nlm.nih.gov/pubmed/33685467 http://dx.doi.org/10.1186/s12957-021-02174-w |
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