ELANE is a promising prognostic biomarker that mediates pyroptosis in gastric cancer

Abstract

BackgroundGastric cancer (GC) is a typical malignant tumor and the main cause of cancer-related deaths. Its pathogenesis involves multiple steps, including pyroptosis, although these steps are still uncertain. Pyroptosis, also known as gasdermin-mediated programmed necrosis, participates in various pathological processes in tumors, including GC. ELANE, which encodes neutrophil elastase, is closely associated with GC. Additionally, ELANE has been implicated in GC cell pyroptosis, but this has not been confirmed. Therefore, investigating the link between ELANE and pyroptosis in GC is warranted. This research uses bioinformatics and experiments to examine the relationship between ELANE, pyroptosis, and GC prognosis. MethodsThe GEO and TCGA databases, along with pyroptosis-related genes, were applied to identify pyroptosis-related differentially expressed genes (DEGs). ELANE was selected via primary screening. Using the median expression level of ELANE as the threshold, pyroptosis-related DEGs were divided into low- and high-ELANE groups. Based on the DEGs in these two groups, GO, KEGG and GSEA analyses were conducted to elucidate the mechanisms of ELANE in GC. Furthermore, we plotted ROC and Kaplan–Meier curves to analyze the clinical and pathological features of ELANE expression. The Nomograms tool was applied to calculate the predictive value of ELANE for the clinical outcomes of GC cases. Immunohistochemical analysis was performed to detect the level of ELANE in GC tissues and to validate whether ELANE was involved in pyroptosis in GC cells through cell experiments. Finally, the immune infiltration of ELANE was investigated, and interaction networks (proteins-ELANE, microRNA-ELANE, and small-molecule drug-ELANE) were constructed. ResultsWe aimed to investigate the expression of the ELANE gene in GC and study the relationship among ELANE, pyroptosis, and the prognosis of patients with GC. Differential expression analysis of gene-expression datasets from TCGA-STAD and GSE49051 revealed that the expression of the ELANE gene was significantly up-regulated in GC. Using STRING network analysis, we identified multiple proteins involved in the occurrence and development of GC, including interactions between ELANE and GSDMC, a member of the gasdermin protein family. Survival analysis showed that ELANE expression levels significantly affected overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS) in patients with GC. Additionally, ROC analysis demonstrated that ELANE was effective in distinguishing GC patients from normal controls (AUC = 0.812). Immunohistochemical analysis showed that ELANE was highly expressed in gastric cancer tissues and was closely related to age, tumor grade, and stage. The cell experiments further confirmed that the high expression of ELANE in gastric cancer cells was associated with pyroptosis. Comprehensive analysis indicated that ELANE could be used as a potential prognostic marker for GC and plays an important role in pyroptosis. ConclusionHigh ELANE expression is related to poor survival and prognosis of patients with GC. It participates in pyroptosis and immune infiltration in GC. Therefore, ELANE is a promising prognostic biomarker for pyroptosis in GC.