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Current Cancer Drug Targets

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ISSN (Online): 1873-5576

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Research Article

Identification of ATM Mutation as a Potential Prognostic Biomarker for Immune Checkpoint Inhibitors Therapy

Author(s): Saijin Cui, Tianyu Chen, Yaning Zhao, Zhuoyun Xiao, Meitong Liu, Xi Huang, Shiru Cao, Rongmiao Zhou, You Li, Xiangran Huo and Na Wang*

Volume 24, Issue 5, 2024

Published on: 20 November, 2023

Page: [501 - 509] Pages: 9

DOI: 10.2174/0115680096250376231025062652

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.

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