Gastric Cancer (GC) is the fifth leading cause of cancer-related death in the world, and in urgent need of specific therapeutic targets to acquire prominent effectiveness. T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) and programmed cell death protein 1 (PD-1) are identified to be abnormally overexpressed in various types of cancers including GC. This study aimed to investigate whether TIGIT and PD-1 could serve as potential prognostic biomarkers for GC. Firstly, TCGA GC dataset analysis and correlation analysis were utilized to inspect the relationship between expression of TIGIT, PD-1 and CD8 + T cells in GC and adjacent normal tissues. Then, flow cytometry was used to verify the data after collecting the peripheral blood, GC and adjacent normal tissues from 150 GC patients. Lastly, quantitative RT-PCR was performed to detect the expression of CD155, CD113, CD112 and TIGIT in six human GC cell lines and 631 GC patients in KM Plotter Database to conduct prognostic analysis. As results, we found that TIGIT and PD-1 were upregulated in GC tissues with high CD8 + T cells infiltration, while correlation analysis indicated they were in high-positive correlation. In addition, the flow cytometry analysis further showed that the high-expression of TIGIT in tumor microenvironment of GC could suppress the function of infiltrative CD8 + T cells, which leads to the escape of GC cells from immune killing. Furthermore, CD155 and CD112 were found abnormally upregulated in GC tissues and cell lines and the high expression of CD155, CD112 and TIGIT demonstrated poor prognosis results. In conclusion, these results provided potential therapeutic targets and prognostic biomarkers for treatment of GC in clinic.

中文翻译：

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TIGIT 和 PD-1 可能作为胃癌的潜在预后生物标志物。

胃癌（GC）是全球第五大癌症相关死亡原因，迫切需要特定的治疗靶点以获得显着疗效。T 细胞免疫球蛋白和免疫受体酪氨酸抑制基序 (ITIM) 结构域 (TIGIT) 和程序性细胞死亡蛋白 1 (PD-1) 被确定在包括 GC 在内的各种类型的癌症中异常过度表达。本研究旨在探讨 TIGIT 和 PD-1 是否可以作为 GC 的潜在预后生物标志物。首先利用TCGA GC数据集分析和相关性分析检测GC及邻近正常组织中TIGIT、PD-1和CD8+T细胞表达的关系。然后，收集150例GC患者的外周血、GC及邻近正常组织后，采用流式细胞术对数据进行验证。最后，采用定量RT-PCR检测KM Plotter数据库中6种人GC细胞系和631例GC患者CD155、CD113、CD112和TIGIT的表达情况，进行预后分析。结果，我们发现 TIGIT 和 PD-1 在具有高 CD8 + T 细胞浸润的 GC 组织中上调，而相关性分析表明它们呈高度正相关。此外，流式细胞术分析进一步表明，GC肿瘤微环境中TIGIT的高表达可抑制浸润性CD8+T细胞的功能，从而导致GC细胞逃避免疫杀伤。此外，在胃癌组织和细胞系中发现 CD155 和 CD112 异常上调，CD155、CD112 和 TIGIT 的高表达表明预后不良。综上所述，