Department of Pathology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
Department of Pathology, School of Basic Medical Sciences and State Key Laboratory of Reproductive Medicine and Key Laboratory of Antibody Technique of National Health Commission, Nanjing Medical University, Nanjing, China.
Gut Liver. 2022 Nov 15;16(6):875-891. doi: 10.5009/gnl210359. Epub 2022 May 25.
BACKGROUND/AIMS: : Epstein-Barr virus-associated gastric cancers (EBVaGCs) have unique molecular and clinicopathological characteristics. The cyclic GMP-AMP synthase-stimulator of interferon genes (STING) pathway is recently recognized as the critical innate immunity against pathogens and tumors. STING is also a master regulator in the cancer-immunity cycle and targeting STING could synergize with existing immune-checkpoint therapies. However, the role of STING in GC, especially in EBVaGC, and its correlation with programmed death-ligand 1 (PD-L1) remain largely unclear.
We collected 78 cases of EBVaGCs and 210 cases of EBV-negative GC (EBVnGC) from a total of 1,443 cases of GC analyzed by EBV-encoded small RNA hybridization. We investigated STING and PD-L1 expression and their concomitant prognostic value in EBVaGCs and EBVnGCs using tissue microarray and immunohistochemistry. The effects of STING and PD-L1 expression on the overall survival of patients with EBVaGC or EBVnGC were assessed by univariate and multivariate analysis.
We found that both STING and PD-L1 exhibited significantly higher expression in the EBVaGCs than that in the EBVnGCs. The expression of STING was positively correlated with that of PD-L1 in EBVaGCs. Simultaneous negative expression of STING and PD-L1, and positive expression of STING were independent prognostic risk factors for EBVaGC and EBVnGC, respectively.
This is the first prognostic retrospective study of STING and PD-L1 expression and the prognosis among EBVaGC and EBVnGC. The expression and prognostic value of STING and PD-L1 are different in the two types of GCs. STING and PD-L1 are promising prognostic biomarkers and therapeutic targets for EBVaGC and EBVnGC.
背景/目的： Epstein-Barr 病毒相关胃癌（EBVaGC）具有独特的分子和临床病理特征。环鸟苷酸-腺苷酸合酶-干扰素基因刺激物（STING）途径最近被认为是对抗病原体和肿瘤的关键固有免疫途径。STING 也是癌症免疫循环中的主要调节剂，靶向 STING 可以与现有的免疫检查点疗法协同作用。然而，STING 在 GC 中的作用，特别是在 EBVaGC 中的作用及其与程序性死亡配体 1（PD-L1）的相关性在很大程度上仍不清楚。
我们从总共 1443 例 GC 中分析的 EBV 编码小 RNA 杂交中收集了 78 例 EBVaGC 和 210 例 EBV 阴性 GC（EBVnGC）。我们使用组织微阵列和免疫组织化学方法研究了 STING 和 PD-L1 在 EBVaGC 和 EBVnGC 中的表达及其伴随的预后价值。通过单因素和多因素分析评估 STING 和 PD-L1 表达对 EBVaGC 或 EBVnGC 患者总生存率的影响。
我们发现 STING 和 PD-L1 在 EBVaGC 中的表达均明显高于 EBVnGC。在 EBVaGC 中，STING 的表达与 PD-L1 的表达呈正相关。同时，STING 和 PD-L1 的阴性表达以及 STING 的阳性表达分别是 EBVaGC 和 EBVnGC 的独立预后危险因素。
这是第一项关于 STING 和 PD-L1 表达及其在 EBVaGC 和 EBVnGC 中的预后的回顾性研究。STING 和 PD-L1 的表达和预后价值在两种 GC 中有所不同。STING 和 PD-L1 是 EBVaGC 和 EBVnGC 有前途的预后生物标志物和治疗靶点。
