Gut Liver.  2022 Nov;16(6):875-891. 10.5009/gnl210359.

Prognostic Perspectives of STING and PD-L1 Expression and Correlation with the Prognosis of Epstein-Barr Virus-Associated Gastric Cancers

Affiliations
  • 1Department of Pathology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
  • 2Department 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.
  • 3Department of Oncology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China.
  • 4Department of Oncology, Jiangsu Cancer Hospital and The Affiliated Cancer Hospital of Nanjing Medical University and Jiangsu Institute of Cancer Research, Nanjing, China.
  • 5Sir Run Run Hospital, Nanjing Medical University, Nanjing, China.

Abstract

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.

Keyword

PD-L1; STING; Epstein-Barr virus; Gastric cancer; Biomarkers
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