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KLF4 loss in hepatocellular carcinoma: Improving prognostic prediction and correlating immune infiltrates
Introduction: Although the molecular mechanisms of Krüpple-like factor 4 (KLF4) as a tumor suppressor in HCC tumorigenesis have been thoroughly examined, its clinical application in terms of precise prognostication and its influence on tumor immune microenvironment in patients with HCC require furth...
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/PMC10017851/ https://www.ncbi.nlm.nih.gov/pubmed/36936440 http://dx.doi.org/10.3389/fgene.2023.1106952 |
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author | Chen, Desheng Zhu, Qi Li, Tiewen Fan, Xuhui Lou, Yichao Zhang, Yi Huang, Kejie Sun, Hongcheng |
author_facet | Chen, Desheng Zhu, Qi Li, Tiewen Fan, Xuhui Lou, Yichao Zhang, Yi Huang, Kejie Sun, Hongcheng |
author_sort | Chen, Desheng |
collection | PubMed |
description | Introduction: Although the molecular mechanisms of Krüpple-like factor 4 (KLF4) as a tumor suppressor in HCC tumorigenesis have been thoroughly examined, its clinical application in terms of precise prognostication and its influence on tumor immune microenvironment in patients with HCC require further investigation. Methods: Bioinformatics and immunohistochemistry (IHC) were used to validate KLF4 expressions in a tissue microarray (TMA) containing HCC samples. Using Cox regression models, independent prognostic factors were identified and employed in the development of nomograms. Decision curve analysis (DCA) demonstrated the superiority of the nomograms. GO and KEGG pathway analyses were applied to the functional study of KLF4. The GSVA program explored the link between KLF4 expression and tumor-infiltrating immune cells, and CAMOIP was used to construct KLF4 expression immune scores. Changes in immune-related gene markers were also investigated in relation to KLF4 expression. The association between immune cell infiltration and KLF4 expression was validated by IHC in TMA. Results: HCC was reported to have a notable depletion of KLF4. The absence of KLF4 was associated with advanced clinicopathological characteristics of HCC and predicted a bad prognosis for patients. Nomograms constructed using KLF4 expression, tumor differentiation, and TNM stage provided a more accurate prognostic assessment of HCC patients than TNM stage alone. KLF4 expression was associated with immunological-related functions, infiltration of macrophages, CD8(+) T cells, and other immune cells, and elevation of immune checkpoints. Higher levels of CD8(+) T cells and macrophage infiltration are associated with increased KLF4 expression in HCC TMA. Conclusion: KLF4 loss in HCC is a prognostic biomarker that influences the tumor immune microenvironment (TIME). |
format | Online Article Text |
id | pubmed-10017851 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-100178512023-03-17 KLF4 loss in hepatocellular carcinoma: Improving prognostic prediction and correlating immune infiltrates Chen, Desheng Zhu, Qi Li, Tiewen Fan, Xuhui Lou, Yichao Zhang, Yi Huang, Kejie Sun, Hongcheng Front Genet Genetics Introduction: Although the molecular mechanisms of Krüpple-like factor 4 (KLF4) as a tumor suppressor in HCC tumorigenesis have been thoroughly examined, its clinical application in terms of precise prognostication and its influence on tumor immune microenvironment in patients with HCC require further investigation. Methods: Bioinformatics and immunohistochemistry (IHC) were used to validate KLF4 expressions in a tissue microarray (TMA) containing HCC samples. Using Cox regression models, independent prognostic factors were identified and employed in the development of nomograms. Decision curve analysis (DCA) demonstrated the superiority of the nomograms. GO and KEGG pathway analyses were applied to the functional study of KLF4. The GSVA program explored the link between KLF4 expression and tumor-infiltrating immune cells, and CAMOIP was used to construct KLF4 expression immune scores. Changes in immune-related gene markers were also investigated in relation to KLF4 expression. The association between immune cell infiltration and KLF4 expression was validated by IHC in TMA. Results: HCC was reported to have a notable depletion of KLF4. The absence of KLF4 was associated with advanced clinicopathological characteristics of HCC and predicted a bad prognosis for patients. Nomograms constructed using KLF4 expression, tumor differentiation, and TNM stage provided a more accurate prognostic assessment of HCC patients than TNM stage alone. KLF4 expression was associated with immunological-related functions, infiltration of macrophages, CD8(+) T cells, and other immune cells, and elevation of immune checkpoints. Higher levels of CD8(+) T cells and macrophage infiltration are associated with increased KLF4 expression in HCC TMA. Conclusion: KLF4 loss in HCC is a prognostic biomarker that influences the tumor immune microenvironment (TIME). Frontiers Media S.A. 2023-03-02 /pmc/articles/PMC10017851/ /pubmed/36936440 http://dx.doi.org/10.3389/fgene.2023.1106952 Text en Copyright © 2023 Chen, Zhu, Li, Fan, Lou, Zhang, Huang and Sun. 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 Chen, Desheng Zhu, Qi Li, Tiewen Fan, Xuhui Lou, Yichao Zhang, Yi Huang, Kejie Sun, Hongcheng KLF4 loss in hepatocellular carcinoma: Improving prognostic prediction and correlating immune infiltrates |
title | KLF4 loss in hepatocellular carcinoma: Improving prognostic prediction and correlating immune infiltrates |
title_full | KLF4 loss in hepatocellular carcinoma: Improving prognostic prediction and correlating immune infiltrates |
title_fullStr | KLF4 loss in hepatocellular carcinoma: Improving prognostic prediction and correlating immune infiltrates |
title_full_unstemmed | KLF4 loss in hepatocellular carcinoma: Improving prognostic prediction and correlating immune infiltrates |
title_short | KLF4 loss in hepatocellular carcinoma: Improving prognostic prediction and correlating immune infiltrates |
title_sort | klf4 loss in hepatocellular carcinoma: improving prognostic prediction and correlating immune infiltrates |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10017851/ https://www.ncbi.nlm.nih.gov/pubmed/36936440 http://dx.doi.org/10.3389/fgene.2023.1106952 |
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