Identifying key genes involved in HBV-related hepatocellular carcinoma: diagnose, prognosis, interaction and immune analysis

Abstract Background Hepatitis B virus associated hepatocellular carcinoma (HBV-HCC) have been a serious global health problem. This study aimed to uncover the key genes in HBV-HCC, and clarity their function, interaction, diagnostic and prognostic value, impacts on immune infltration and potential d...

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Main Authors: Yan Li, Sa-Sa Liu, Hua-Rong Jing, Hong-Wei Qian, Rui-Cheng Li
Format: Article
Language:English
Published: Springer 2025-08-01
Series:Discover Oncology
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Online Access:https://doi.org/10.1007/s12672-025-03320-6
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author Yan Li
Sa-Sa Liu
Hua-Rong Jing
Hong-Wei Qian
Rui-Cheng Li
author_facet Yan Li
Sa-Sa Liu
Hua-Rong Jing
Hong-Wei Qian
Rui-Cheng Li
author_sort Yan Li
collection DOAJ
description Abstract Background Hepatitis B virus associated hepatocellular carcinoma (HBV-HCC) have been a serious global health problem. This study aimed to uncover the key genes in HBV-HCC, and clarity their function, interaction, diagnostic and prognostic value, impacts on immune infltration and potential drugs targeting these genes. Methods Four gene expression datasets totally containing 117 paired tumor tissues and adjacent control tissues were selected from the GEO database and used to screen the differentially expressed genes (DEGs). Function analysis were performed by using GO and KEGG enrichment. STRING and cytoscape were used to analyze protein-protein interaction (PPI) and screen hub gene. Survival analysis and receiver operator characteristic (ROC) curve were used to explore the prognostic and diagnostic value of key genes. Immune infiltration analysis were performed by CIBERSORT algorithm. Drug–Gene Interaction Database (DGIdb) was used to screen the potential drug that affect hub genes. Results Overall, 234 shared DEGs were screened from four GSE datasets, which were mainly enrichment in cell growth regulation, epoxygenase P450 pathway, cellular response to multiple ion, xenobiotic metabolic process and complement activation. Six hub genes (HMMR, NDC80, CDK1, EZH2, ESR1, FOXM1) were screen by PPI analysis. ESR1 was down-regulated and associated with favorable prognosis in HBV-HCC, while HMMR, NDC80, CDK1 and EZH2 were up-regulated and correlation with shorter overall survival. Furthermore, ROC analysis and nomogram demonstrated the high diagnostic performance of NDC80, CDK1 and EZH2. Immune infiltration analysis showed that there were significant difference of several immune cell types between tumor and control tissues, including T cells, monocyte/macrophage and dendritic cells. There were significant correlation between hub genes with immune infiltration. Finally, DGIdb analysis showed there were several approved or new drugs that interaction with HMMR, CDK1, ESR1 and EZH2. Conclusion Six hug-genes are closely related to the HBV-HCC development, which involved in multiple biological progress and immune infiltration. Among them, NDC80, CDK1, EZH2 could severed as markers with good diagnostic and prognostic value. Notably, several approved drugs interaction with hub genes might be potential drug used for HBV-HCC therapy.
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spelling doaj-art-e85c53210a3240adaf3c0c54f0353a8e2025-08-20T03:43:22ZengSpringerDiscover Oncology2730-60112025-08-0116111310.1007/s12672-025-03320-6Identifying key genes involved in HBV-related hepatocellular carcinoma: diagnose, prognosis, interaction and immune analysisYan Li0Sa-Sa Liu1Hua-Rong Jing2Hong-Wei Qian3Rui-Cheng Li4School of Medical Laboratory, North Henan Medical UniversityDepartment of Clinical Laboratory, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Clinical Laboratory, Tangdu Hospital, Fourth Military Medical UniversityDepartment of Clinical Laboratory, Tangdu Hospital, Fourth Military Medical UniversityDepartment of Clinical Laboratory, Tangdu Hospital, Fourth Military Medical UniversityAbstract Background Hepatitis B virus associated hepatocellular carcinoma (HBV-HCC) have been a serious global health problem. This study aimed to uncover the key genes in HBV-HCC, and clarity their function, interaction, diagnostic and prognostic value, impacts on immune infltration and potential drugs targeting these genes. Methods Four gene expression datasets totally containing 117 paired tumor tissues and adjacent control tissues were selected from the GEO database and used to screen the differentially expressed genes (DEGs). Function analysis were performed by using GO and KEGG enrichment. STRING and cytoscape were used to analyze protein-protein interaction (PPI) and screen hub gene. Survival analysis and receiver operator characteristic (ROC) curve were used to explore the prognostic and diagnostic value of key genes. Immune infiltration analysis were performed by CIBERSORT algorithm. Drug–Gene Interaction Database (DGIdb) was used to screen the potential drug that affect hub genes. Results Overall, 234 shared DEGs were screened from four GSE datasets, which were mainly enrichment in cell growth regulation, epoxygenase P450 pathway, cellular response to multiple ion, xenobiotic metabolic process and complement activation. Six hub genes (HMMR, NDC80, CDK1, EZH2, ESR1, FOXM1) were screen by PPI analysis. ESR1 was down-regulated and associated with favorable prognosis in HBV-HCC, while HMMR, NDC80, CDK1 and EZH2 were up-regulated and correlation with shorter overall survival. Furthermore, ROC analysis and nomogram demonstrated the high diagnostic performance of NDC80, CDK1 and EZH2. Immune infiltration analysis showed that there were significant difference of several immune cell types between tumor and control tissues, including T cells, monocyte/macrophage and dendritic cells. There were significant correlation between hub genes with immune infiltration. Finally, DGIdb analysis showed there were several approved or new drugs that interaction with HMMR, CDK1, ESR1 and EZH2. Conclusion Six hug-genes are closely related to the HBV-HCC development, which involved in multiple biological progress and immune infiltration. Among them, NDC80, CDK1, EZH2 could severed as markers with good diagnostic and prognostic value. Notably, several approved drugs interaction with hub genes might be potential drug used for HBV-HCC therapy.https://doi.org/10.1007/s12672-025-03320-6HBV-HCCDifferentially expressed genesDiagnosePrognosisImmune infiltration
spellingShingle Yan Li
Sa-Sa Liu
Hua-Rong Jing
Hong-Wei Qian
Rui-Cheng Li
Identifying key genes involved in HBV-related hepatocellular carcinoma: diagnose, prognosis, interaction and immune analysis
Discover Oncology
HBV-HCC
Differentially expressed genes
Diagnose
Prognosis
Immune infiltration
title Identifying key genes involved in HBV-related hepatocellular carcinoma: diagnose, prognosis, interaction and immune analysis
title_full Identifying key genes involved in HBV-related hepatocellular carcinoma: diagnose, prognosis, interaction and immune analysis
title_fullStr Identifying key genes involved in HBV-related hepatocellular carcinoma: diagnose, prognosis, interaction and immune analysis
title_full_unstemmed Identifying key genes involved in HBV-related hepatocellular carcinoma: diagnose, prognosis, interaction and immune analysis
title_short Identifying key genes involved in HBV-related hepatocellular carcinoma: diagnose, prognosis, interaction and immune analysis
title_sort identifying key genes involved in hbv related hepatocellular carcinoma diagnose prognosis interaction and immune analysis
topic HBV-HCC
Differentially expressed genes
Diagnose
Prognosis
Immune infiltration
url https://doi.org/10.1007/s12672-025-03320-6
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