Data_Sheet 1_v1_Exploration of the Tumor Immune Landscape and Identification of Two Novel Immunotherapy-Related Genes for Epstein-Barr virus-associated Gastric Carcinoma via Integrated Bioinformatics Analysis.pdf

Epstein–Barr virus (EBV)-associated gastric carcinoma (EBVaGC) is a specific molecular subtype of gastric carcinoma with a high proportion of tumor-infiltrating lymphocytes. It is a highly immunogenic tumor that may benefit from immunotherapy. Hence, it is imperative to analyze the immune landscape and identify immunotherapy biomarkers for EBVaGC. In our study, we investigated the immune landscape and identified 10 hub genes for EBVaGC via integrated bioinformatics analysis. We found that EBVaGC expressed more immune-related genes, including common immune checkpoints and human leukocyte antigen (HLA) genes than EBV-negative gastric carcinoma (EBVnGC). The immune score in EBVaGC was higher, which means EBVaGC has greater immune cell infiltration. Ten hub genes (CD4, STAT1, FCGR3A, IL10, C1QA, CXCL9, CXCL10, CXCR6, PD-L1, and CCL18) were detected as candidate biomarkers for EBVaGC. Two hub genes, CXCL9 and CXCR6, were identified as novel immunotherapy-related genes. Taken together, the results of our comprehensive analysis of the immune microenvironment of EBVaGC revealed its unique immune landscape, demonstrating that it is a highly immunogenic tumor. Moreover, we identified hub genes that may serve as potential immunotherapy biomarkers for EBVaGC.

EB病毒（Epstein–Barr virus, EBV）相关胃癌（EBVaGC）是胃癌的特定分子亚型，其肿瘤浸润淋巴细胞占比颇高。该肿瘤具有高度免疫原性，有望从免疫治疗中获益，因此解析EBVaGC的免疫景观并筛选免疫治疗生物标志物实属必要。本研究通过整合生物信息学分析，对EBVaGC的免疫景观展开探究并鉴定出10个核心基因。研究发现，相较于EB病毒阴性胃癌（EBVnGC），EBVaGC的免疫相关基因表达水平更高，其中涵盖常见免疫检查点基因与人类白细胞抗原（HLA）基因。EBVaGC的免疫评分更高，意味着其免疫细胞浸润程度更强。本研究鉴定出10个可作为EBVaGC候选生物标志物的核心基因，分别为CD4、STAT1、FCGR3A、IL10、C1QA、CXCL9、CXCL10、CXCR6、PD-L1及CCL18，其中CXCL9与CXCR6这两个核心基因被鉴定为新型免疫治疗相关基因。综上，本研究对EBVaGC免疫微环境的综合分析结果揭示了其独特的免疫景观，证实该肿瘤为高度免疫原性肿瘤，同时筛选出的核心基因可作为EBVaGC潜在的免疫治疗生物标志物。