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Identification and Validation of Three Core Genes in p53 Signaling Pathway in Hepatitis B Virus-Related Hepatocellular Carcinoma
Yutian Chong
Third Affiliated Hospital of Sun Yat-Sen University
Corresponding Author
ORCiD: https://orcid.org/0000-0001-8215-4393
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This work is licensed under a CC BY 4.0 License. Read Full License
Background：Hepatocellular carcinoma (HCC) is a common cancer and the leading cause is persistent hepatitis B virus 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. The GEO2R online tool and Venn diagram software were applied to analyze commonly differentially expressed genes. 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 gene expression in tumor tissues from HBV related HCC patients, HBV-related liver cell lines, and transfection si-p53 and knock-out p53 liver cancer cell lines. Finally, the prediction of the ceRNA network was constructed with R software.
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 highly-expressed samples of three core genes were all enriched in the p53 signaling pathway in a validation dataset(P<0.0001). Expression of these three core genes were consistently higher in tumor tissue samples (P<0.0001) and liver cancer cell lines (P<0.05). However, transfection si-p53 and knock-out p53 liver cancer cell lines had lower expression (P<0.05). LncRNAs, including NEAT1, MALAT1, XIST, AC021078.1, and SNHG16, were identified by close interactions with core genes.
Conclusions: CCNB1, CDK1, and RRM2 were enriched in the p53 signaling pathway and could be potential biomarkers and therapeutic targets for HBV-related HCC.
Keywords
hepatocellular carcinoma (HCC), hepatitis B virus (HBV), biomarker, bioinformatical analysis, p53 signaling pathway
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This is a list of supplementary files associated with this preprint. Click to download.
- supplementary1.tif
Supplementary figure 1. The prognostic information of other 12 genes
- supplementaryfigure2.tif
Supplement figure 2. The expression level of other 12 genes
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Reviewer #2 agreed
On 07 Jan, 2021
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Reviewer #1 agreed
On 28 Dec, 2020
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Editor invited
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This preprint is under consideration at World Journal of Surgical Oncology. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Identification and Validation of Three Core Genes in p53 Signaling Pathway in Hepatitis B Virus-Related Hepatocellular Carcinoma
Yutian Chong
Third Affiliated Hospital of Sun Yat-Sen University
Corresponding Author
ORCiD: https://orcid.org/0000-0001-8215-4393
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 30 Dec, 2020
No community comments so far
Reviewer #2 agreed
On 07 Jan, 2021
Reviewers invited
Invitations sent on 28 Dec, 2020
Reviewer #1 agreed
On 28 Dec, 2020
Editor assigned
On 26 Dec, 2020
Editor invited
On 26 Dec, 2020
Submission checks complete
On 26 Dec, 2020
First submitted
On 22 Dec, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background：Hepatocellular carcinoma (HCC) is a common cancer and the leading cause is persistent hepatitis B virus 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. The GEO2R online tool and Venn diagram software were applied to analyze commonly differentially expressed genes. 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 gene expression in tumor tissues from HBV related HCC patients, HBV-related liver cell lines, and transfection si-p53 and knock-out p53 liver cancer cell lines. Finally, the prediction of the ceRNA network was constructed with R software.
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 highly-expressed samples of three core genes were all enriched in the p53 signaling pathway in a validation dataset(P<0.0001). Expression of these three core genes were consistently higher in tumor tissue samples (P<0.0001) and liver cancer cell lines (P<0.05). However, transfection si-p53 and knock-out p53 liver cancer cell lines had lower expression (P<0.05). LncRNAs, including NEAT1, MALAT1, XIST, AC021078.1, and SNHG16, were identified by close interactions with core genes.
Conclusions: CCNB1, CDK1, and RRM2 were enriched in the p53 signaling pathway and could be potential biomarkers and therapeutic targets for HBV-related HCC.
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