Neutrophil elastase as a potential biomarker related to the prognosis of gastric cancer and immune cell infiltration in the tumor immune microenvironment

Abstract

AbstractExploring biomarkers interrelated the tumor immune microenvironment (TIME) provides novel ideas for predicting the prognosis of gastric cancer (GC) and developing new treatment strategies. We analyzed the differential gene expression levels between the high and low StromalScore and ImmuneScore groups. Neutrophil elastase (ELANE) was evaluated as a potential biomarker by conducting intersection analysis of the protein–protein interaction network and univariate Cox regression analysis. The expression of ELANE was evaluated by immunohistochemistry. Its prognostic value was evaluated using Kaplan–Meier (K–M) survival curves and multivariate Cox regression analysis and its potential biological molecular mechanism was examined by gene set enrichment analysis (GSEA). We applied the CIBERSORT computing method to analyze the relationship between ELANE and tumor immune-infiltrating cells (TIICs). K–M survival curve showed that higher ELANE expression was closely related to shorter overall survival. The Cox regression analysis indicated that the high expression of ELANE was an independent prognostic risk factor in patients with GC. The GSEA revealed that genes in the ELANE high-expression group were involved in the signaling pathways regulating immune response; genes in the ELANE low-expression group were involved in the signaling pathways that regulate metabolism. ELANE might be participate in the change of TIME from immunodominant to metabolically dominant and its expression was closely related to tumor mutation burden and multiple TIICs. ELANE is a potential biomarker for predicting the GC patients’ survival and prognosis. It influences the tumor immune cell infiltration in the TIME, and affects the TIME to maintain their immune status.