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Comprehensive analysis of cuproptosis-related prognostic gene signature and tumor immune microenvironment in HCC
Background: Copper is an indispensable mineral element involved in many physiological metabolic processes. Cuproptosis is associated with a variety of cancer such as hepatocellular carcinoma (HCC). The objective of this study was to examine the relationships between the expression of cuproptosis-rel...
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/PMC9986498/ https://www.ncbi.nlm.nih.gov/pubmed/36891150 http://dx.doi.org/10.3389/fgene.2023.1094793 |
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author | Qin, Haotian Sheng, Weibei Zhang, Geng Yang, Qi Yao, Sen Yue, Yaohang Zhang, Peng Zhu, Yuanchao Wang, Qichang Chen, Yixiao Zeng, Hui Weng, Jian Yu, Fei Yang, Jun |
author_facet | Qin, Haotian Sheng, Weibei Zhang, Geng Yang, Qi Yao, Sen Yue, Yaohang Zhang, Peng Zhu, Yuanchao Wang, Qichang Chen, Yixiao Zeng, Hui Weng, Jian Yu, Fei Yang, Jun |
author_sort | Qin, Haotian |
collection | PubMed |
description | Background: Copper is an indispensable mineral element involved in many physiological metabolic processes. Cuproptosis is associated with a variety of cancer such as hepatocellular carcinoma (HCC). The objective of this study was to examine the relationships between the expression of cuproptosis-related genes (CRGs) and tumor characteristics, including prognosis and microenvironment of HCC. Methods: The differentially expressed genes (DEGs) between high and low CRGs expression groups in HCC samples were identified, and further were analyzed for functional enrichment analysis. Then, CRGs signature of HCC was constructed and analyzed utilizing LASSO and univariate and multivariate Cox regression analysis. Prognostic values of CRGs signature were evaluated by Kaplan-Meier analysis, independent prognostic analysis and nomograph. The expression of prognostic CRGs was verified by Real-time quantitative PCR (RT-qPCR) in HCC cell lines. In addition, the relationships between prognostic CRGs expression and the immune infiltration, tumor microenvironment, antitumor drugs response and m6A modifications were further explored using a series of algorithms in HCC. Finally, ceRNA regulatory network based on prognostic CRGs was constructed. Results: The DEGs between high and low CRG expression groups in HCC were mainly enriched in focal adhesion and extracellular matrix organization. Besides, we constructed a prognostic model that consists of CDKN2A, DLAT, DLST, GLS, and PDHA1 CRGs for predicting the survival likelihood of HCC patients. And the elevated expression of these five prognostic CRGs was substantially in HCC cell lines and associated with poor prognosis. Moreover, immune score and m6A gene expression were higher in the high CRG expression group of HCC patients. Furthermore, prognostic CRGs have higher mutation rates in HCC, and are significantly correlated with immune cell infiltration, tumor mutational burden, microsatellite instability, and anti-tumor drug sensitivity. Then, eight lncRNA-miRNA-mRNA regulatory axes that affected the progression of HCC were predicted. Conclusion: This study demonstrated that the CRGs signature could effectively evaluate prognosis, tumor immune microenvironment, immunotherapy response and predict lncRNA-miRNA-mRNA regulatory axes in HCC. These findings extend our knowledge of cuproptosis in HCC and may inform novel therapeutic strategies for HCC. |
format | Online Article Text |
id | pubmed-9986498 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-99864982023-03-07 Comprehensive analysis of cuproptosis-related prognostic gene signature and tumor immune microenvironment in HCC Qin, Haotian Sheng, Weibei Zhang, Geng Yang, Qi Yao, Sen Yue, Yaohang Zhang, Peng Zhu, Yuanchao Wang, Qichang Chen, Yixiao Zeng, Hui Weng, Jian Yu, Fei Yang, Jun Front Genet Genetics Background: Copper is an indispensable mineral element involved in many physiological metabolic processes. Cuproptosis is associated with a variety of cancer such as hepatocellular carcinoma (HCC). The objective of this study was to examine the relationships between the expression of cuproptosis-related genes (CRGs) and tumor characteristics, including prognosis and microenvironment of HCC. Methods: The differentially expressed genes (DEGs) between high and low CRGs expression groups in HCC samples were identified, and further were analyzed for functional enrichment analysis. Then, CRGs signature of HCC was constructed and analyzed utilizing LASSO and univariate and multivariate Cox regression analysis. Prognostic values of CRGs signature were evaluated by Kaplan-Meier analysis, independent prognostic analysis and nomograph. The expression of prognostic CRGs was verified by Real-time quantitative PCR (RT-qPCR) in HCC cell lines. In addition, the relationships between prognostic CRGs expression and the immune infiltration, tumor microenvironment, antitumor drugs response and m6A modifications were further explored using a series of algorithms in HCC. Finally, ceRNA regulatory network based on prognostic CRGs was constructed. Results: The DEGs between high and low CRG expression groups in HCC were mainly enriched in focal adhesion and extracellular matrix organization. Besides, we constructed a prognostic model that consists of CDKN2A, DLAT, DLST, GLS, and PDHA1 CRGs for predicting the survival likelihood of HCC patients. And the elevated expression of these five prognostic CRGs was substantially in HCC cell lines and associated with poor prognosis. Moreover, immune score and m6A gene expression were higher in the high CRG expression group of HCC patients. Furthermore, prognostic CRGs have higher mutation rates in HCC, and are significantly correlated with immune cell infiltration, tumor mutational burden, microsatellite instability, and anti-tumor drug sensitivity. Then, eight lncRNA-miRNA-mRNA regulatory axes that affected the progression of HCC were predicted. Conclusion: This study demonstrated that the CRGs signature could effectively evaluate prognosis, tumor immune microenvironment, immunotherapy response and predict lncRNA-miRNA-mRNA regulatory axes in HCC. These findings extend our knowledge of cuproptosis in HCC and may inform novel therapeutic strategies for HCC. Frontiers Media S.A. 2023-02-20 /pmc/articles/PMC9986498/ /pubmed/36891150 http://dx.doi.org/10.3389/fgene.2023.1094793 Text en Copyright © 2023 Qin, Sheng, Zhang, Yang, Yao, Yue, Zhang, Zhu, Wang, Chen, Zeng, Weng, Yu and Yang. 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 Qin, Haotian Sheng, Weibei Zhang, Geng Yang, Qi Yao, Sen Yue, Yaohang Zhang, Peng Zhu, Yuanchao Wang, Qichang Chen, Yixiao Zeng, Hui Weng, Jian Yu, Fei Yang, Jun Comprehensive analysis of cuproptosis-related prognostic gene signature and tumor immune microenvironment in HCC |
title | Comprehensive analysis of cuproptosis-related prognostic gene signature and tumor immune microenvironment in HCC |
title_full | Comprehensive analysis of cuproptosis-related prognostic gene signature and tumor immune microenvironment in HCC |
title_fullStr | Comprehensive analysis of cuproptosis-related prognostic gene signature and tumor immune microenvironment in HCC |
title_full_unstemmed | Comprehensive analysis of cuproptosis-related prognostic gene signature and tumor immune microenvironment in HCC |
title_short | Comprehensive analysis of cuproptosis-related prognostic gene signature and tumor immune microenvironment in HCC |
title_sort | comprehensive analysis of cuproptosis-related prognostic gene signature and tumor immune microenvironment in hcc |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9986498/ https://www.ncbi.nlm.nih.gov/pubmed/36891150 http://dx.doi.org/10.3389/fgene.2023.1094793 |
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