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.
Keywords: CD8+ T cells infiltration; Gastric cancer; Programmed cell death ligand 1; Programmed cell death protein 1; TIGIT.
Copyright © 2020. Published by Elsevier GmbH.