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Cuproptosis regulator-mediated patterns associated with immune infiltration features and construction of cuproptosis-related signatures to guide immunotherapy

BACKGROUND: Liver hepatocellular carcinoma (HCC) is a prevalent cancer that lacks a sufficiently efficient approach to guide immunotherapy. Additionally, cuproptosis is a recently identified regulated cell death program that is triggered by copper ionophores. However, its possible significance in tu...

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Autores principales: Wang, Gongjun, Xiao, Ruoxi, Zhao, Shufen, Sun, Libin, Guo, Jing, Li, Wenqian, Zhang, Yuqi, Bian, Xiaoqian, Qiu, Wensheng, Wang, Shasha
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9559227/
https://www.ncbi.nlm.nih.gov/pubmed/36248857
http://dx.doi.org/10.3389/fimmu.2022.945516
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author Wang, Gongjun
Xiao, Ruoxi
Zhao, Shufen
Sun, Libin
Guo, Jing
Li, Wenqian
Zhang, Yuqi
Bian, Xiaoqian
Qiu, Wensheng
Wang, Shasha
author_facet Wang, Gongjun
Xiao, Ruoxi
Zhao, Shufen
Sun, Libin
Guo, Jing
Li, Wenqian
Zhang, Yuqi
Bian, Xiaoqian
Qiu, Wensheng
Wang, Shasha
author_sort Wang, Gongjun
collection PubMed
description BACKGROUND: Liver hepatocellular carcinoma (HCC) is a prevalent cancer that lacks a sufficiently efficient approach to guide immunotherapy. Additionally, cuproptosis is a recently identified regulated cell death program that is triggered by copper ionophores. However, its possible significance in tumor immune cell infiltration is still unclear. METHODS: Cuproptosis subtypes in HCC were identified using unsupervised consensus cluster analysis based on 10 cuproptosis regulators expressions, and a cuproptosis-related risk signature was generated using univariate and LASSO Cox regression and validated using the ICGC data. Moreover, the relationship between signature and tumor immune microenvironment (TME) was studied through tumor immunotherapy responsiveness, immune cell infiltration, and tumor stem cell analysis. Finally, clinical specimens were analyzed using immunohistochemistry to verify the expression of the three genes in the signature. RESULTS: Two subtypes of cuproptosis regulation were observed in HCC, with different immune cell infiltration features. Genes expressed differentially between the two cuproptosis clusters in the TCGA were determined and used to construct a risk signature that was validated using the ICGC cohort. Greater immune and stromal cell infiltration were observed in the high-risk group and were associated with unfavorable prognosis. Elevated risk scores were linked with higher RNA stemness scores (RNAss) and tumor mutational burden (TMB), together with a greater likelihood of benefitting from immunotherapy. CONCLUSION: It was found that cuproptosis regulatory patterns may play important roles in the heterogeneity of immune cell infiltration. The risk signature associated with cuproptosis can assess each patient’s risk score, leading to more individualized and effective immunotherapy.
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spelling pubmed-95592272022-10-14 Cuproptosis regulator-mediated patterns associated with immune infiltration features and construction of cuproptosis-related signatures to guide immunotherapy Wang, Gongjun Xiao, Ruoxi Zhao, Shufen Sun, Libin Guo, Jing Li, Wenqian Zhang, Yuqi Bian, Xiaoqian Qiu, Wensheng Wang, Shasha Front Immunol Immunology BACKGROUND: Liver hepatocellular carcinoma (HCC) is a prevalent cancer that lacks a sufficiently efficient approach to guide immunotherapy. Additionally, cuproptosis is a recently identified regulated cell death program that is triggered by copper ionophores. However, its possible significance in tumor immune cell infiltration is still unclear. METHODS: Cuproptosis subtypes in HCC were identified using unsupervised consensus cluster analysis based on 10 cuproptosis regulators expressions, and a cuproptosis-related risk signature was generated using univariate and LASSO Cox regression and validated using the ICGC data. Moreover, the relationship between signature and tumor immune microenvironment (TME) was studied through tumor immunotherapy responsiveness, immune cell infiltration, and tumor stem cell analysis. Finally, clinical specimens were analyzed using immunohistochemistry to verify the expression of the three genes in the signature. RESULTS: Two subtypes of cuproptosis regulation were observed in HCC, with different immune cell infiltration features. Genes expressed differentially between the two cuproptosis clusters in the TCGA were determined and used to construct a risk signature that was validated using the ICGC cohort. Greater immune and stromal cell infiltration were observed in the high-risk group and were associated with unfavorable prognosis. Elevated risk scores were linked with higher RNA stemness scores (RNAss) and tumor mutational burden (TMB), together with a greater likelihood of benefitting from immunotherapy. CONCLUSION: It was found that cuproptosis regulatory patterns may play important roles in the heterogeneity of immune cell infiltration. The risk signature associated with cuproptosis can assess each patient’s risk score, leading to more individualized and effective immunotherapy. Frontiers Media S.A. 2022-09-29 /pmc/articles/PMC9559227/ /pubmed/36248857 http://dx.doi.org/10.3389/fimmu.2022.945516 Text en Copyright © 2022 Wang, Xiao, Zhao, Sun, Guo, Li, Zhang, Bian, Qiu and Wang 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 Immunology
Wang, Gongjun
Xiao, Ruoxi
Zhao, Shufen
Sun, Libin
Guo, Jing
Li, Wenqian
Zhang, Yuqi
Bian, Xiaoqian
Qiu, Wensheng
Wang, Shasha
Cuproptosis regulator-mediated patterns associated with immune infiltration features and construction of cuproptosis-related signatures to guide immunotherapy
title Cuproptosis regulator-mediated patterns associated with immune infiltration features and construction of cuproptosis-related signatures to guide immunotherapy
title_full Cuproptosis regulator-mediated patterns associated with immune infiltration features and construction of cuproptosis-related signatures to guide immunotherapy
title_fullStr Cuproptosis regulator-mediated patterns associated with immune infiltration features and construction of cuproptosis-related signatures to guide immunotherapy
title_full_unstemmed Cuproptosis regulator-mediated patterns associated with immune infiltration features and construction of cuproptosis-related signatures to guide immunotherapy
title_short Cuproptosis regulator-mediated patterns associated with immune infiltration features and construction of cuproptosis-related signatures to guide immunotherapy
title_sort cuproptosis regulator-mediated patterns associated with immune infiltration features and construction of cuproptosis-related signatures to guide immunotherapy
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9559227/
https://www.ncbi.nlm.nih.gov/pubmed/36248857
http://dx.doi.org/10.3389/fimmu.2022.945516
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