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.

中文翻译：

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与食管腺癌相关的诊断和治疗性炎症反应相关基因特征的鉴定

本研究的目的是鉴定与食管腺癌（EAC）炎症反应相关的关键调控基因，并寻找新的诊断和治疗选择。我们从基因表达综合数据库下载了本研究的数据集 GSE72874。使用加权基因共表达网络分析（WGCNA）和差异表达基因（DEG）分析来寻找EAC中常见的炎症反应相关基因（IRRG）。使用 CIBERSORTx 在线数据库分析正常和肿瘤免疫浸润之间的关系。最终鉴定出920个DEG，其中5个基因是与EAC相关的关键IRRG，包括三个下调基因GNA15、MXD1和NOD2，以及两个下调基因PLAUR和TIMP1。进一步研究发现，巴雷特食管（BE）中 GNA15、MXD1 和 NOD2 下调，PLAUR 和 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的表达量减少，而PLAUR和TIMP1的表达量在乙醇处理后增加。与正常食管组织相比，EAC中浆细胞、巨噬细胞M0、巨噬细胞M1、巨噬细胞M2、活化的树突状细胞、活化的肥大细胞等免疫细胞浸润明显增多，而T细胞CD4记忆静息、T细胞等免疫细胞浸润明显增多。滤泡辅助细胞、静息的 NK 细胞和静息的树突状细胞显着减少。受试者工作特征曲线表明，GNA15、MXD1、NOD2、PLAUR 和 TIMP1 表达在诊断健康对照的 EAC 方面表现良好。GNA15、MXD1、NOD2、PLAUR 和 TIMP1 被鉴定和验证为早期诊断的新型潜在生物标志物，并且可能是治疗 EAC 的新分子靶点。