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赖氨氧化酶(LOX)及其甲基化影响疾病预后并与食管癌(ESCA)中的肿瘤相关巨噬细胞(TAM)浸润相关。

LOX and Its Methylation Impact Prognosis of Diseases and Correlate with TAM Infiltration in ESCA.

作者信息

Wu Chuanqiang, Jiang Bin, Wu Zixiang, Dong Lingjun, Sun Keyi, Wu Ming

机构信息

Department of Thoracic Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jie-Fang Road, Hangzhou 310009, Zhejiang, China.

Department of Thoracic Surgery, Shaoxing People's Hospital, 568-Zhongxing North Road, Shaoxing 312000, Zhejiang, China.

出版信息

J Oncol. 2022 Aug 31;2022:5111237. doi: 10.1155/2022/5111237. eCollection 2022.

Abstract

BACKGROUND

ESCA is one of the digestive tract tumors with a high fatality. It is implicated in an intricate gene regulation process, but the pathogenesis remains ambiguous.

METHODS

The study used the packages of Limma from R software to analyze DEGs of ESCA in the GEO database and TCGA database. We employed the DAVID website for enrichment analysis, and the string database constructed the PPI network. Hub genes were identified from ESCA DEGs with Cytoscape MCODE. We evaluated the clinical relevance of LOX expression and its DNA methylation in the cBioPortal database and explored the roles of LOX in ESCA immunity, especially immune cell infiltration levels and immune checkpoint expression, by immunedeconv package of R software.

CONCLUSIONS

The overexpression of LOX in ESCA is regulated by DNA hypomethylation; LOX overexpression or LOX hypomethylation can predict a worse prognosis in patients with ESCA. Besides, LOX may be involved in TIME regulation, promoting the infiltration levels and function of TAM. Hence, high LOX expression affected by DNA hypomethylation has an essential role in patients with ESCA, which may become an effective prognostic marker and therapeutic target.

摘要

背景

食管癌是致死率较高的消化道肿瘤之一。它涉及复杂的基因调控过程,但其发病机制仍不明确。

方法

本研究使用R软件中的Limma软件包分析基因表达综合数据库(GEO数据库)和癌症基因组图谱(TCGA数据库)中食管癌的差异表达基因(DEGs)。我们利用DAVID网站进行富集分析,并通过STRING数据库构建蛋白质-蛋白质相互作用(PPI)网络。利用Cytoscape软件的分子复合物检测(MCODE)功能从食管癌差异表达基因中鉴定出枢纽基因。我们在cbioportal数据库中评估赖氨氧化酶(LOX)表达及其DNA甲基化的临床相关性,并通过R软件的免疫反卷积软件包探讨LOX在食管癌免疫中的作用,特别是免疫细胞浸润水平和免疫检查点表达。

结论

食管癌中LOX的过表达受DNA低甲基化调控;LOX过表达或LOX低甲基化可预测食管癌患者预后较差。此外,LOX可能参与肿瘤免疫微环境(TIME)调节,促进肿瘤相关巨噬细胞(TAM)的浸润水平和功能。因此,受DNA低甲基化影响的高LOX表达在食管癌患者中具有重要作用,这可能成为有效的预后标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ffd/9452977/c0f9af50d7e5/JO2022-5111237.001.jpg

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