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Identification of novel prognostic biomarkers in the TF-enhancer-target regulatory network in hepatocellular carcinoma and immune infiltration analysis
Background: Hepatocellular carcinoma (HCC) remains notorious for its high malignancy, poor prognosis and high mortality. The exploration of novel therapeutic agents for HCC has remained challenging due to its complex aetiology. Therefore, it is necessary to elucidate the pathogenesis and mechanism o...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10090374/ https://www.ncbi.nlm.nih.gov/pubmed/37065474 http://dx.doi.org/10.3389/fgene.2023.1158341 |
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author | Yan, Jianing Ye, Guoliang Shao, Yongfu Zhou, Hanxuan |
author_facet | Yan, Jianing Ye, Guoliang Shao, Yongfu Zhou, Hanxuan |
author_sort | Yan, Jianing |
collection | PubMed |
description | Background: Hepatocellular carcinoma (HCC) remains notorious for its high malignancy, poor prognosis and high mortality. The exploration of novel therapeutic agents for HCC has remained challenging due to its complex aetiology. Therefore, it is necessary to elucidate the pathogenesis and mechanism of HCC for clinical intervention. Methods: We collected data from several public data portals and systematically analysed the association between transcription factors (TFs), eRNA-associated enhancers and downstream targets. We next filtered the prognostic genes and established a novel prognosis-related nomogram model. Moreover, we explored the potential mechanisms of the identified prognostic genes. The expression level was validated by several ways. Results: We first constructed a significant TF-enhancer-target regulatory network and identified DAPK1 as a coregulatory differentially expressed prognosis-related gene. We combined common clinicopathological factors and built a prognostic nomogram model for HCC. We found that our regulatory network was correlated with the processes of synthesizing various substances. Moreover, we explored the role of DAPK1 in HCC and found that it was associated with immune cell infiltration and DNA methylation. Several immunostimulators and targeting drugs could be promising immune therapy targets. The tumor immune microenvironment was analyzed. Finally, the lower DAPK1 expression in HCC was validated via the GEO database, UALCAN cohort, and qRT-PCR. Conclusion: In conclusion, we established a significant TF-enhancer-target regulatory network and identified downregulated DAPK1 as an important prognostic and diagnostic gene in HCC. Its potential biological functions and mechanisms were annotated using bioinformatics tools. |
format | Online Article Text |
id | pubmed-10090374 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-100903742023-04-13 Identification of novel prognostic biomarkers in the TF-enhancer-target regulatory network in hepatocellular carcinoma and immune infiltration analysis Yan, Jianing Ye, Guoliang Shao, Yongfu Zhou, Hanxuan Front Genet Genetics Background: Hepatocellular carcinoma (HCC) remains notorious for its high malignancy, poor prognosis and high mortality. The exploration of novel therapeutic agents for HCC has remained challenging due to its complex aetiology. Therefore, it is necessary to elucidate the pathogenesis and mechanism of HCC for clinical intervention. Methods: We collected data from several public data portals and systematically analysed the association between transcription factors (TFs), eRNA-associated enhancers and downstream targets. We next filtered the prognostic genes and established a novel prognosis-related nomogram model. Moreover, we explored the potential mechanisms of the identified prognostic genes. The expression level was validated by several ways. Results: We first constructed a significant TF-enhancer-target regulatory network and identified DAPK1 as a coregulatory differentially expressed prognosis-related gene. We combined common clinicopathological factors and built a prognostic nomogram model for HCC. We found that our regulatory network was correlated with the processes of synthesizing various substances. Moreover, we explored the role of DAPK1 in HCC and found that it was associated with immune cell infiltration and DNA methylation. Several immunostimulators and targeting drugs could be promising immune therapy targets. The tumor immune microenvironment was analyzed. Finally, the lower DAPK1 expression in HCC was validated via the GEO database, UALCAN cohort, and qRT-PCR. Conclusion: In conclusion, we established a significant TF-enhancer-target regulatory network and identified downregulated DAPK1 as an important prognostic and diagnostic gene in HCC. Its potential biological functions and mechanisms were annotated using bioinformatics tools. Frontiers Media S.A. 2023-03-29 /pmc/articles/PMC10090374/ /pubmed/37065474 http://dx.doi.org/10.3389/fgene.2023.1158341 Text en Copyright © 2023 Yan, Ye, Shao and Zhou. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Yan, Jianing Ye, Guoliang Shao, Yongfu Zhou, Hanxuan Identification of novel prognostic biomarkers in the TF-enhancer-target regulatory network in hepatocellular carcinoma and immune infiltration analysis |
title | Identification of novel prognostic biomarkers in the TF-enhancer-target regulatory network in hepatocellular carcinoma and immune infiltration analysis |
title_full | Identification of novel prognostic biomarkers in the TF-enhancer-target regulatory network in hepatocellular carcinoma and immune infiltration analysis |
title_fullStr | Identification of novel prognostic biomarkers in the TF-enhancer-target regulatory network in hepatocellular carcinoma and immune infiltration analysis |
title_full_unstemmed | Identification of novel prognostic biomarkers in the TF-enhancer-target regulatory network in hepatocellular carcinoma and immune infiltration analysis |
title_short | Identification of novel prognostic biomarkers in the TF-enhancer-target regulatory network in hepatocellular carcinoma and immune infiltration analysis |
title_sort | identification of novel prognostic biomarkers in the tf-enhancer-target regulatory network in hepatocellular carcinoma and immune infiltration analysis |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10090374/ https://www.ncbi.nlm.nih.gov/pubmed/37065474 http://dx.doi.org/10.3389/fgene.2023.1158341 |
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