Dose-effect relationship between blood cGAS and STING expression and CD44 positivity in cancer tissues of patients with bladder transitional cell carcinoma

Hu Wanyan; Wang Yi; Qin Xiaoyan; Zheng Zhiang

doi:10.3969/j.issn.1671-6450.2025.02.017

Abstract：Objective To explore the dose-effect relationship between the expression of cyclic GMP-AMP syn-thase(cGAS)and stimulator of interferon genes(STING)in the blood of patients with urothelial carcinoma of the bladder(UCB)and the positivity of CD44 in cancer tissues.Methods Sixty patients with UCB in our hospital from October 2022 to May 2024 were selected as the study group,60 patients with inverted papilloma of bladder during the same period were se-lected as control group Ⅰ,and 60 healthy patients were selected as control group Ⅱ.The expression of cGAS and STING in blood of the 3 groups and the expression of CD44,a tumor stem cell marker,in the study group and control group Ⅰ were compared.Spearman rank correlation coefficient was used to analyze the correlation between blood cGAS and STING ex-pression and tissue CD44 expression in study group and control group Ⅰ.The study group divided CD44 expression into positive patients and negative patients and analyzed the independent risk factors of CD44 positive tissues by multiple Lo-gistic regression.The dose-effect relationship between expression of cGAS and STING in blood and positive CD44 in tissue was analyzed by restricted cubic spline diagram.Results The expression of cGAS and STING in the study group was high-er than that in control group Ⅰ and control group Ⅱ,and that in control group Ⅰ was higher than that in control group Ⅱ(F/P=194.740/＜0.001,142.937/＜0.001).The score and positive expression rate of CD44 of tumor stem cells in the study group were higher than those in the control group Ⅰ(t/x2/P=18.463/＜0.001,67.222/＜0.001).The expressions of cGAS(r=-0.638,P＜0.001)and STING(r=-0.717,P＜0.001)in the study group were moderately negatively correlated with the scores of CD44 in tissues.The expressions of cGAS(r=-0.299,P=0.020)and STING(r=-0.291,P=0.024)expression had low correlation with tissue CD44 score.Lymph node metastasis and depth of tumor invasion were independent risk fac-tor for CD44 positive tissue,and cGAS mRNA and STING mRNA were independent protective factors for CD44 positive tis-sue[OR(95％CI)=2.558(1289-5.076),2.870(1.313-6275),0.673(0518-0.874),0.696(0.529-0.915)].There was a nonlin-ear dose-effect relationship between expression of cGAS and STING in blood and CD44 positive in tissue.When cGAS mR-NA＞2.15 and STING mRNA＞1.75,the risk of CD44 positive in tissue significantly reduced.Conclusion In UCB pa-tients,the expression of cGAS and STING in the blood increases,and when both of them increase significantly,they have an inhibitory effect on the expression of CD44 in UCB tissues.