Identification of ATM Mutation as a Potential Prognostic Biomarker for Immune Checkpoint Inhibitors Therapy.
Curr Cancer Drug Targets
; 24(5): 501-509, 2024.
Article
em En
| MEDLINE
| ID: mdl-38804343
ABSTRACT
BACKGROUND:
Ataxia telangiectasia mutated (ATM), an apical DNA damage response gene, is a commonly mutated gene in tumors, and its mutation could strengthen tumor immunogenicity and alter the expression of PD-L1, which potentially contributes to immune checkpoint inhibitors (ICIs) therapy.METHODS:
The characteristics of ATM mutation and its relationship with the ICIs-treated clinical prognosis have been analyzed comprehensively in this paper. The overall frequency of ATM mutations has been found to be 4% (554/10953) in the cancer genome atlas (TCGA) cohort.RESULTS:
Both the TMB and MSI levels in patients with ATM mutations were significantly higher than those in patients without mutations (P < 0.0001). The median TMB was positively correlated with the frequency of ATM mutations (r = 0.54, P = 0.003). In the TCGA cohort, patients with ATM mutations had better clinical benefits in terms of overall survival (OS, hazard ratio (HR) = 0.736, 95% CI = 0.623 - 0.869), progression-free survival (PFS, HR = 0.761, 95% CI = 0.652 - 0.889), and disease-free survival (DFS, HR = 0.686, 95% CI = 0.512 - 0.919)] than patients without ATM mutations. Subsequently, the verification results showed ATM mutations to be significantly correlated with longer OS in ICIs-treated patients (HR = 0.710, 95% CI = 0.544 - 0.928). Further exploration indicated ATM mutation to be significantly associated with regulated anti-tumor immunity (P < 0.05).CONCLUSION:
Our findings highlight the value of ATM mutation as a promising biomarker to predict ICIs therapy in multiple tumors.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Biomarcadores Tumorais
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Proteínas Mutadas de Ataxia Telangiectasia
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Inibidores de Checkpoint Imunológico
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Mutação
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Neoplasias
Limite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Curr Cancer Drug Targets
Assunto da revista:
ANTINEOPLASICOS
/
NEOPLASIAS
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China