Zhou Qirui, Jia Ruinan, Chen Jinlin, Tan Yang, Ma Yuechan, Luan Mengfan, Sheng Xue, Han Xiao, Li Shuying, Lu Fei, Ji Chunyan, Wang Dongmei, Ye Jingjing
Department of Hematology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong University, Jinan, China.
Shandong Key Laboratory of Hematological Diseases and Immune Microenvironment, Qilu Hospital of Shandong University, Shandong University, Jinan, China.
Front Immunol. 2025 Dec 16;16:1725218. doi: 10.3389/fimmu.2025.1725218. eCollection 2025.
Diffuse large B cell lymphoma (DLBCL) is a highly heterogeneous lymphoid neoplasm characterized by diverse gene expression profiles and genetic alterations, resulting in substantial variations in clinical features and response to therapy. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway plays a central role in innate immune response and affects the development of DLBCL. However, the relationship between genetic polymorphisms in genes involved in the cGAS-STING-mediated signaling pathway and their role in DLBCL remains underexplored.
A total of 147 patients with DLBCL and 247 healthy controls were recruited. Single nucleotide polymorphism (SNP) genotyping was conducted using the MassARRAY platform. We evaluated the associations between the selected SNPs and DLBCL susceptibility, clinical features, and survival.
In our study, TREX1 rs11797 and CXCL10 rs4508917 showed significant association with DLBCL susceptibility. IFNB1 rs1051922 was correlated with white blood cell (WBC) and monocyte count at diagnosis. TREX1 rs11797 and IFNB1 rs1051922 were associated with chemotherapy response in DLBCL. Moreover, PRMT1 rs975484 and CXCL10 rs8878 were associated with the overall survival of patients with DLBCL. Notably, PRMT1 rs975484 was also correlated with hemoglobin (HGB) level, and may serve as an independent favorable prognostic factor in DLBCL.
Our findings suggest that SNPs involved in cGAS-STING-mediated type I interferon pathway may influence DLBCL susceptibility, treatment response, and prognosis, highlighting their potential as biomarkers for risk stratification and for guiding individualized disease monitoring.
弥漫性大B细胞淋巴瘤（DLBCL）是一种高度异质性的淋巴瘤，其特征在于多样的基因表达谱和基因改变，导致临床特征和对治疗的反应存在显著差异。环磷酸鸟苷-腺苷酸合成酶（cGAS）-干扰素基因刺激物（STING）通路在先天免疫反应中起核心作用，并影响DLBCL的发展。然而，参与cGAS-STING介导的信号通路的基因中的遗传多态性与其在DLBCL中的作用之间的关系仍未得到充分研究。
共招募了147例DLBCL患者和247名健康对照。使用MassARRAY平台进行单核苷酸多态性（SNP）基因分型。我们评估了所选SNP与DLBCL易感性、临床特征和生存率之间的关联。
在我们的研究中，TREX1 rs11797和CXCL10 rs4508917与DLBCL易感性显著相关。IFNB1 rs1051922与诊断时的白细胞（WBC）和单核细胞计数相关。TREX1 rs11797和IFNB1 rs1051922与DLBCL的化疗反应相关。此外，PRMT1 rs975484和CXCL10 rs8878与DLBCL患者的总生存期相关。值得注意的是，PRMT1 rs975484也与血红蛋白（HGB）水平相关，并且可能是DLBCL中一个独立的有利预后因素。
我们的研究结果表明，参与cGAS-STING介导的I型干扰素通路的SNP可能影响DLBCL的易感性、治疗反应和预后，突出了它们作为风险分层生物标志物和指导个体化疾病监测的潜力。
