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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2023.1158341/full |
| _version_ | 1797857910615703552 |
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| author | Jianing Yan Jianing Yan Guoliang Ye Guoliang Ye Yongfu Shao Yongfu Shao Hanxuan Zhou |
| author_facet | Jianing Yan Jianing Yan Guoliang Ye Guoliang Ye Yongfu Shao Yongfu Shao Hanxuan Zhou |
| author_sort | Jianing Yan |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-09T21:04:30Z |
| format | Article |
| id | doaj.art-d0cd696d416f44de84c45168d1e9c490 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-09T21:04:30Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-d0cd696d416f44de84c45168d1e9c4902023-03-29T04:38:14ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-03-011410.3389/fgene.2023.11583411158341Identification of novel prognostic biomarkers in the TF-enhancer-target regulatory network in hepatocellular carcinoma and immune infiltration analysisJianing Yan0Jianing Yan1Guoliang Ye2Guoliang Ye3Yongfu Shao4Yongfu Shao5Hanxuan Zhou6Department of Gastroenterology, The First Affiliated Hospital of Ningbo University, Ningbo, ChinaDepartment of Gastroenterology, Institute of Digestive Disease of Ningbo University, Ningbo, ChinaDepartment of Gastroenterology, The First Affiliated Hospital of Ningbo University, Ningbo, ChinaDepartment of Gastroenterology, Institute of Digestive Disease of Ningbo University, Ningbo, ChinaDepartment of Gastroenterology, The First Affiliated Hospital of Ningbo University, Ningbo, ChinaDepartment of Gastroenterology, Institute of Digestive Disease of Ningbo University, Ningbo, ChinaDepartment of Pharmacy, Yinzhou Integrated TCM and Western Medicine Hospital, Ningbo, ChinaBackground: 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.https://www.frontiersin.org/articles/10.3389/fgene.2023.1158341/fullhepatocellular carcinomaDAPk1eRNAenhancerprognosisregulatory network |
| spellingShingle | Jianing Yan Jianing Yan Guoliang Ye Guoliang Ye Yongfu Shao Yongfu Shao Hanxuan Zhou Identification of novel prognostic biomarkers in the TF-enhancer-target regulatory network in hepatocellular carcinoma and immune infiltration analysis Frontiers in Genetics hepatocellular carcinoma DAPk1 eRNA enhancer prognosis regulatory network |
| 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 | hepatocellular carcinoma DAPk1 eRNA enhancer prognosis regulatory network |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2023.1158341/full |
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