Unveiling the role of FTO polymorphisms in predicting response to immune checkpoint inhibitors: A retrospective study

Abstract

BackgroundIdentifying 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. MethodThis 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. ResultsPharmacogenomic 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). ConclusionWe identified FTO gene polymorphisms associated with treatment outcomes of ICI treatment in patients with multiple solid cancers, which might serve as potential predictive biomarkers.