Identification of a Diagnosis and Therapeutic Inflammatory Response-Related Gene Signature Associated with Esophageal Adenocarcinoma.

IF 1.5 4区 医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Yang Xie, Jun Li, Qing Tao, Chunyan Zeng, Youxiang Chen
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引用次数: 0

Abstract

The purpose of this study is to identify the key regulatory genes related to the inflammatory response of esophageal adenocarcinoma (EAC) and to find new diagnosis and therapeutic options. We downloaded the dataset GSE72874 from the Gene Expression Omnibus database for this study. Weighted gene co-expression network analysis (WGCNA) and differentially expressed genes (DEGs) analysis were used to find common inflammatory response-related genes (IRRGs) in EAC. The relationship between normal and tumor immune infiltration was analyzed using an online database of CIBERSORTx. Finally, 920 DEGs were identified, of which 5 genes were key IRRGs associated with EAC, including three down-regulated genes GNA15, MXD1, and NOD2, and two down-regulated genes PLAUR and TIMP1. Further research found that GNA15, MXD1, and NOD2 were down-regulated, PLAUR and TIMP1 were up-regulated in Barrett's esophagus (BE). In addition, we found that the expression of GNA15 and MXD1 in normal esophageal squamous epithelial cells decreased after ethanol treatment, while the expression of PLAUR and TIMP1 increased after ethanol treatment. Compared with normal esophageal tissue, immune cells infiltrated such as plasma cells, macrophages M0, macrophages M1, macrophages M2, dendritic cells activated, and mast cells activated were significantly increased in EAC, while immune cells infiltrated such as T cells CD4 memory resting, T cells follicular helper, NK cells resting, and dendritic cells resting were significantly reduced. The receiver operating characteristic curve indicated that GNA15, MXD1, NOD2, PLAUR and TIMP1 expression had a performed well in diagnosing EAC from healthy control. GNA15, MXD1, NOD2, PLAUR and TIMP1 were identified and validated as novel potential biomarkers for early diagnosis and may be new molecular targets for treatment of EAC.

与食管腺癌相关的诊断和治疗炎症反应相关基因特征的鉴定。
本研究的目的是确定食管腺癌(EAC)炎症反应相关的关键调控基因,并寻找新的诊断和治疗方案。我们从Gene Expression Omnibus数据库下载数据集GSE72874用于本研究。采用加权基因共表达网络分析(WGCNA)和差异表达基因(DEGs)分析寻找EAC中常见的炎症反应相关基因(IRRGs)。利用CIBERSORTx在线数据库分析正常与肿瘤免疫浸润的关系。最终共鉴定出920个deg,其中5个基因为EAC相关的关键IRRGs,包括3个下调基因GNA15、MXD1和NOD2,以及2个下调基因PLAUR和TIMP1。进一步研究发现,Barrett食管(BE)中GNA15、MXD1、NOD2下调,PLAUR、TIMP1上调。此外,我们发现乙醇处理后正常食管鳞状上皮细胞中GNA15和MXD1的表达降低,而PLAUR和TIMP1的表达升高。与正常食管组织相比,EAC中浸润的浆细胞、巨噬细胞M0、巨噬细胞M1、巨噬细胞M2、活化树突状细胞、活化肥大细胞等免疫细胞明显增加,浸润的T细胞CD4记忆静息、T细胞滤泡辅助、NK细胞静息、树突状细胞静息等免疫细胞明显减少。受试者工作特征曲线显示GNA15、MXD1、NOD2、PLAUR和TIMP1的表达对健康对照的EAC有较好的诊断价值。GNA15、MXD1、NOD2、PLAUR和TIMP1被发现并验证为早期诊断的潜在生物标志物,可能成为治疗EAC的新分子靶点。
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来源期刊
Critical Reviews in Eukaryotic Gene Expression
Critical Reviews in Eukaryotic Gene Expression 生物-生物工程与应用微生物
CiteScore
2.70
自引率
0.00%
发文量
67
审稿时长
1 months
期刊介绍: Critical ReviewsTM in Eukaryotic Gene Expression presents timely concepts and experimental approaches that are contributing to rapid advances in our mechanistic understanding of gene regulation, organization, and structure within the contexts of biological control and the diagnosis/treatment of disease. The journal provides in-depth critical reviews, on well-defined topics of immediate interest, written by recognized specialists in the field. Extensive literature citations provide a comprehensive information resource. Reviews are developed from an historical perspective and suggest directions that can be anticipated. Strengths as well as limitations of methodologies and experimental strategies are considered.
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