Gene polymorphisms of molecules of the cGAS‑STING signalling pathway are associated with AML in Chinese patients  

作　　者：Yuechan Ma Dongmei Wang Lei Feng Mengyuan Chang Mingying Li Guangqiang Meng Yuyan Wu Fei Lu Tao Sun Chunyan Ji Jingjing Ye 

机构地区：[1]Department of Hematology,Qilu Hospital,Shandong University,Jinan,China [2]Shandong Key Laboratory of Immunohematology,Qilu Hospital,Shandong University,Jinan,China

出　　处：《Holistic Integrative Oncology》2024年第1期539-548,共10页整合肿瘤学(英文)

基　　金：supported by grants from the Distinguished Taishan Scholars in Climbing Plan(tspd20210321);Taishan Scholars-Distinguished Experts(tstp20230653);the National Natural Science Foundation of China(82000165;82370165);the Key Program of Natural Science Foundation of Shandong Province(ZR2021MH302);the Horizontal Subject of Shandong University(6010121004).

摘　　要：Purpose The aim of this study was to explore the relationships between single-nucleotide polymorphisms(SNPs)of crucial molecules in the cGAS-STING signalling pathway and the susceptibility to,induction chemotherapy response of,and prognosis of acute myeloid leukaemia(AML)in Chinese patients.Methods Thirteen SNPs of crucial molecules in the cGAS-STING signalling pathway were genotyped in 262 AML patients using the Sequenom MassARRAY system.The associations of SNPs with susceptibility,and induction chemo-therapy response were analysed using the chi-square test or Fisher’s exact test and univariate binary logistic regres-sion,the connection of SNPs with prognosis of AML was analysed using the log-rank test,and Kaplan–Meier curves were applied for survival estimation.Results In our study,gene polymorphisms of cGAS-STING signalling pathway molecules could be vitally associated with AML.In the recessive model,the cGAS rs311678 gene polymorphism could be closely related to AML suscep-tibility(CC vs.TT+TC,odds ratio(OR)=0.480,95%confidence interval(CI)=0.260–0.889,p=0.020).Moreover,IKKA rs3808917 might be associated with the WBC count,cGAS rs311678 could be associated with the bone marrow(BM)blast percentage,and NF-κB rs1056890 under codominant and recessive models could be connected with the HGB level.Patients who were STING rs7380272 TT/CT carriers was likely to have higher insensitivity to induction chemo-therapy than CC carriers(TT+CT vs.CC,OR=2.917,95%CI=1.073–7.929,p=0.036).Survival analysis indicated that the IKKB rs3747811 TT genotype might be associated with decreased overall survival(OS)(p<0.05).Conclusions SNPs of molecules in the cGAS-STING signalling pathway could be significantly associated with AML.The cGAS rs311678 gene polymorphism could be associated with AML susceptibility,the STING rs7380272 variant might be related to induction chemotherapy response,and IKKB rs3747811 tended to be associated with AML overall survival.Moreover,IKKA rs3808917 could be associated with the WBC count,cGAS rs31167

关 键 词：Acute myeloid leukaemia cGAS-STING signalling pathway Single-nucleotide polymorphisms PROGNOSIS 

分 类 号：R73[医药卫生—肿瘤]