Prognostic Perspectives of STING and PD-L1 Expression and Correlation with the Prognosis of Epstein-Barr Virus-Associated Gastric Cancers
Qi Sun,
Yao Fu,
Xiaobing Chen,
Lin Li,
Hongyan Wu,
Yixuan Liu,
Haojun Xu,
Guoren Zhou,
Xiangshan Fan,
Hongping Xia
Affiliations
Qi Sun
Department of Pathology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
Yao Fu
Department of Pathology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
Xiaobing Chen
Department of Oncology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China
Lin Li
Department of Pathology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
Hongyan Wu
Department of Pathology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
Yixuan Liu
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
Haojun Xu
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
Guoren Zhou
Department of Oncology, Jiangsu Cancer Hospital and The Affiliated Cancer Hospital of Nanjing Medical University and Jiangsu Institute of Cancer Research, Nanjing, China
Xiangshan Fan
Department of Pathology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
Hongping Xia
Department of Pathology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
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. Methods: 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 in situ 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. Results: 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. Conclusions: 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.
