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Predictive Value of KDM5C Alterations for Immune Checkpoint Inhibitors Treatment Outcomes in Patients With Cancer

Lysine (K)-specific demethylase 5C (KDM5C) plays a significant role in the tumor cell proliferation, invasion, drug resistance and the regulation of tumor-related gene expression. Here, we aimed to investigate its predictive value in patients with cancers received immune checkpoint inhibitors (ICIs)...

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Autores principales: Chen, Xiao-Juan, Ren, Ai-Qun, Zheng, Liang, Zheng, En-Dian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8089485/
https://www.ncbi.nlm.nih.gov/pubmed/33953726
http://dx.doi.org/10.3389/fimmu.2021.664847
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author Chen, Xiao-Juan
Ren, Ai-Qun
Zheng, Liang
Zheng, En-Dian
author_facet Chen, Xiao-Juan
Ren, Ai-Qun
Zheng, Liang
Zheng, En-Dian
author_sort Chen, Xiao-Juan
collection PubMed
description Lysine (K)-specific demethylase 5C (KDM5C) plays a significant role in the tumor cell proliferation, invasion, drug resistance and the regulation of tumor-related gene expression. Here, we aimed to investigate its predictive value in patients with cancers received immune checkpoint inhibitors (ICIs). We explored the predictive value of KDM5C alterations and the association between KDM5C alteration and immune landscape by using published cohort with clinical outcome and sequenced data from online database. The frequency of KDM5C alterations was 2.1% across 48045 tumor samples with different cancers from 185 studies. KDM5C alterations were correlated with markedly inferior overall survival (OS, 53 vs. 102 months, P<0.0001) than those without. However, in ICI-treated group, patients with KDM5C alterations had a substantially prolonged OS than the wild-type group (not reached vs. 18 months, P=0.0041). The predictive value of KDM5C alterations for ICI treatment outcome was not observed in patients with microsatellite-stable tumors (P=0.2875). Intriguingly, patients with non-small-cell lung cancer and KDM5C alterations receiving ICI had the better progression-free survival than wild type group (13.2 vs. 3.2 months, P=0.0762). Mechanistically, KDM5C altered tumors had dramatically higher TMB level and was associated with significantly higher level of CD8+ T cell infiltration and T effector signature. In conclusion, KDM5C alterations was correlated with enhanced tumor immunogenicity and inflamed anti-tumor immunity, thus resulting in better treatment outcome in cancer patients receiving ICIs.
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spelling pubmed-80894852021-05-04 Predictive Value of KDM5C Alterations for Immune Checkpoint Inhibitors Treatment Outcomes in Patients With Cancer Chen, Xiao-Juan Ren, Ai-Qun Zheng, Liang Zheng, En-Dian Front Immunol Immunology Lysine (K)-specific demethylase 5C (KDM5C) plays a significant role in the tumor cell proliferation, invasion, drug resistance and the regulation of tumor-related gene expression. Here, we aimed to investigate its predictive value in patients with cancers received immune checkpoint inhibitors (ICIs). We explored the predictive value of KDM5C alterations and the association between KDM5C alteration and immune landscape by using published cohort with clinical outcome and sequenced data from online database. The frequency of KDM5C alterations was 2.1% across 48045 tumor samples with different cancers from 185 studies. KDM5C alterations were correlated with markedly inferior overall survival (OS, 53 vs. 102 months, P<0.0001) than those without. However, in ICI-treated group, patients with KDM5C alterations had a substantially prolonged OS than the wild-type group (not reached vs. 18 months, P=0.0041). The predictive value of KDM5C alterations for ICI treatment outcome was not observed in patients with microsatellite-stable tumors (P=0.2875). Intriguingly, patients with non-small-cell lung cancer and KDM5C alterations receiving ICI had the better progression-free survival than wild type group (13.2 vs. 3.2 months, P=0.0762). Mechanistically, KDM5C altered tumors had dramatically higher TMB level and was associated with significantly higher level of CD8+ T cell infiltration and T effector signature. In conclusion, KDM5C alterations was correlated with enhanced tumor immunogenicity and inflamed anti-tumor immunity, thus resulting in better treatment outcome in cancer patients receiving ICIs. Frontiers Media S.A. 2021-04-19 /pmc/articles/PMC8089485/ /pubmed/33953726 http://dx.doi.org/10.3389/fimmu.2021.664847 Text en Copyright © 2021 Chen, Ren, Zheng and Zheng 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
Chen, Xiao-Juan
Ren, Ai-Qun
Zheng, Liang
Zheng, En-Dian
Predictive Value of KDM5C Alterations for Immune Checkpoint Inhibitors Treatment Outcomes in Patients With Cancer
title Predictive Value of KDM5C Alterations for Immune Checkpoint Inhibitors Treatment Outcomes in Patients With Cancer
title_full Predictive Value of KDM5C Alterations for Immune Checkpoint Inhibitors Treatment Outcomes in Patients With Cancer
title_fullStr Predictive Value of KDM5C Alterations for Immune Checkpoint Inhibitors Treatment Outcomes in Patients With Cancer
title_full_unstemmed Predictive Value of KDM5C Alterations for Immune Checkpoint Inhibitors Treatment Outcomes in Patients With Cancer
title_short Predictive Value of KDM5C Alterations for Immune Checkpoint Inhibitors Treatment Outcomes in Patients With Cancer
title_sort predictive value of kdm5c alterations for immune checkpoint inhibitors treatment outcomes in patients with cancer
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8089485/
https://www.ncbi.nlm.nih.gov/pubmed/33953726
http://dx.doi.org/10.3389/fimmu.2021.664847
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