Identification and validation of three core genes in p53 signaling pathway in hepatitis B virus-related hepatocellular carcinoma

World Journal of Surgical Oncology

Xinhua Li¹  Wenli Xu¹  Jing Cao¹  Yusheng Jie¹  Siqi Huang¹  Mingxue Yu¹  Jiahui Pang¹  Yutian Chong¹  Jiao Gong² 

[1] Department of Infectious Diseases and Key Laboratory of Liver Disease of Guangdong Province, Third Affiliated Hospital of Sun Yat-sen University, 510630, Guangzhou, Guangdong Province, China;Department of Laboratory Medicine, Third Affiliated Hospital of Sun Yat-sen University, 510630, Guangzhou, Guangdong Province, China;

关键词: Hepatocellular carcinoma (HCC);    Hepatitis B virus (HBV);    Biomarker;    Bioinformatical analysis;    p53 signaling pathway;   

DOI  :  10.1186/s12957-021-02174-w

来源: Springer

【 摘 要 】

BackgroundHepatocellular 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.MethodsGene 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.ResultsFifteen 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).ConclusionsCCNB1, CDK1, and RRM2 were enriched in the p53 signaling pathway and could be potential biomarkers and therapeutic targets for HBV-related HCC.

【 授权许可】

CC BY