关键词: Clinical prognosis ELANE Gastric cancer Immune cells Pyroptosis

来  源:   DOI:10.1016/j.heliyon.2024.e34360   PDF(Pubmed)

Abstract:
UNASSIGNED: Gastric 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.
UNASSIGNED: The 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.
UNASSIGNED: We 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.
UNASSIGNED: High 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.
摘要:
胃癌(GC)是典型的恶性肿瘤,是癌症相关死亡的主要原因。其发病机制涉及多个步骤,包括焦亡,尽管这些步骤仍然不确定。焦亡,也被称为gasdermin介导的程序性坏死,参与肿瘤的各种病理过程,包括GC。伊兰,它编码中性粒细胞弹性蛋白酶,与GC密切相关。此外,ELANE与GC细胞焦亡有关,但这还没有得到证实。因此,在GC中研究ELANE和焦亡之间的联系是有必要的。本研究利用生物信息学和实验来检验ELANE,焦亡,和GC预后。
GEO和TCGA数据库,以及与焦亡相关的基因,用于鉴定与焦亡相关的差异表达基因(DEGs)。通过初级筛选选择ELANE。使用ELANE的中位数表达水平作为阈值,与解热相关的DEGs分为低ELANE和高ELANE组。根据这两组的DEG,GO,进行KEGG和GSEA分析以阐明ELANE在GC中的作用机制。此外,我们绘制了ROC和Kaplan-Meier曲线来分析ELANE表达的临床和病理特征。应用Nomograms工具来计算ELANE对GC病例的临床结果的预测值。进行免疫组织化学分析以检测GC组织中ELANE的水平,并通过细胞实验验证ELANE是否参与GC细胞的焦亡。最后,研究了ELANE的免疫浸润,和相互作用网络(蛋白质-埃兰,microRNA-ELANE,和小分子药物-ELANE)被构建。
我们旨在研究ELANE基因在GC中的表达,并研究ELANE基因与GC,焦亡,以及GC患者的预后。来自TCGA-STAD和GSE49051的基因表达数据集的差异表达分析显示,ELANE基因的表达在GC中显著上调。使用STRING网络分析,我们确定了多种蛋白质参与GC的发生和发展,包括ELANE和GSDMC之间的相互作用,gasdermin蛋白家族的成员。生存分析显示ELANE表达水平显著影响总生存(OS),无病生存率(DFS),GC患者的无进展生存期(PFS)。此外,ROC分析表明ELANE可有效区分GC患者与正常对照(AUC=0.812)。免疫组织化学分析显示ELANE在胃癌组织中高表达,且与年龄密切相关,肿瘤分级,和舞台。细胞实验进一步证实ELANE在胃癌细胞中的高表达与细胞凋亡有关。综合分析表明,ELANE可作为GC的潜在预后标志物,在焦亡中起重要作用。
ELANE高表达与GC患者的不良生存和预后有关。它参与GC的焦亡和免疫浸润。因此,ELANE是GC中焦亡的有希望的预后生物标志物。
公众号