Unveiling the role of FTO polymorphisms in predicting response to immune checkpoint inhibitors: A retrospective study.
Int Immunopharmacol
; 133: 112142, 2024 May 30.
Article
em En
| MEDLINE
| ID: mdl-38669948
ABSTRACT
BACKGROUND:
Identifying patients who can benefit from immune checkpoint inhibitors (ICIs) is a critical challenge in immunotherapy. This study aimed to investigate the association between fat mass and obesity-associated protein (FTO) polymorphisms and ICIs treatment outcomes.METHOD:
This retrospective study was conducted on 371 patients with malignant tumors who received ICIs treatment and were followed-up for a minimum duration of 12 months. Seven variants in FTO gene were genotyped using the Sequenome MassARRAY platform, and their associations with ICIs treatment outcomes were analyzed.RESULTS:
Pharmacogenomic research revealed that individuals carrying the rs11075995AT/TT genotype were more likely to benefit from ICIs treatment compare to TT genotype. Cox regression analysis showed that rs1125338TT carriers exhibited a shorter progression-free survival (PFS, hazard ratio (HR) = 1.72, 95 % confidence interval (CI) = 1.12-2.46), while rs12596638GG carriers experienced extended PFS (HR = 0.71, 95 % CI = 0.50-0.99). Multiple Cox regression analysis indicated that rs12596638GG (HR = 6.81, 95 %CI = 1.20-38.56) and rs1125338CC (HR = 1.78, 95 %CI = 0.07-0.45), rs12600192CC (HR = 0.13, 95 %CI = 0.037-0.44) genotypes were independently associated with overall survival (OS) after adjusting clinical characteristics. Furthermore, patients with rs12600192CC genotype had a lower risk of severe irAEs compared to those with GG/GC genotypes (P < 0.01).CONCLUSION:
We identified FTO gene polymorphisms associated with treatment outcomes of ICI treatment in patients with multiple solid cancers, which might serve as potential predictive biomarkers.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polimorfismo de Nucleotídeo Único
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Dioxigenase FTO Dependente de alfa-Cetoglutarato
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Inibidores de Checkpoint Imunológico
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Neoplasias
Limite:
Adult
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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:
Int Immunopharmacol
Assunto da revista:
ALERGIA E IMUNOLOGIA
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FARMACOLOGIA
Ano de publicação:
2024
Tipo de documento:
Article