| Summary: | Immune checkpoint inhibitors (ICIs) therapy has been successfully utilized in the treatment of multiple tumors, but only a fraction of patients with gastric cancer (GC) could greatly benefit from it. A recent study has shown that the tumor microenvironment (TME) can greatly affect the effect of immunotherapy in GC. In this study, we established a novel immune risk signature (IRS) for prognosis and predicting response to ICIs in GC based on the TCGA-STAD dataset. Characterization of the TME was explored and further validated to reveal the underlying survival mechanisms and the potential therapeutic targets of GC. The GC patients were stratified into high- and low-risk groups based on the IRS. Patients in the high-risk group, associated with poorer outcomes, were characterized by significantly higher immune function. Further analysis showed higher T cell immune dysfunction and probability of potential immune escape. In vivo, we detected the expressions of <i>SERPINE1</i> by the quantitative real-time polymerase chain reaction (qPCR)in tumor tissues and adjacent normal tissues. In vitro, knockdown of <i>SERPINE1</i> significantly attenuated malignant biological behaviors of tumor cells in GC. Our signature can effectively predict the prognosis and response to immunotherapy in patients with GC.
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