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ECE2 是一个与 m6A 修饰相关的预后生物标志物,参与肺腺癌的免疫浸润。

ECE2 is a prognostic biomarker associated with m6A modification and involved in immune infiltration of lung adenocarcinoma.

机构信息

Department of Nuclear Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, China.

Department of Infection Control, Taihe Hospital, Hubei University of Medicine, Shiyan, China.

出版信息

Front Endocrinol (Lausanne). 2022 Oct 10;13:1013238. doi: 10.3389/fendo.2022.1013238. eCollection 2022.

Abstract

BACKGROUND

The targeted therapy for lung cancer relies on prognostic genes and requires further research. No research has been conducted to determine the effect of endothelin-converting enzyme 2 (ECE2) in lung cancer.

METHODS

We analyzed the expression of ECE2 in lung adenocarcinoma (LUAD) and normal adjacent tissues and its relationship with clinicopathological characteristics from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus database (GEO). Immunohistochemical staining was used to further validate the findings. GO/KEGG enrichment analysis and gene set enrichment analysis (GSEA) of ECE2 co-expression were performed using R software. Data from TIMER, the GEPIA database, and TCGA were analyzed to determine the relationship between ECE2 expression and LUAD immune infiltration. To investigate the relationship between ECE2 expression levels and LUAD m6A modification, TCGA data and GEO data were analyzed.

RESULTS

ECE2 is highly expressed in various cancers including LUAD. ECE2 showed high accuracy in distinguishing tumor and normal sample results. The expression level of ECE2 in LUAD was significantly correlated with tumor stage and prognosis. GO/KEGG enrichment analysis showed that ECE2 was closely related to mitochondrial gene expression, ATPase activity and cell cycle. GSEA analysis showed that ECE2-related differential gene enrichment pathways were related to mitotic cell cycle, MYC pathway, PLK1 pathway, DNA methylation pathway, HIF1A pathway and Oxidative stress-induced cellular senescence. Analysis of the TIMER, GEPIA database, and TCGA datasets showed that ECE2 expression levels were significantly negatively correlated with B cells, CD4+ cells, M2 macrophages, neutrophils, and dendritic cells. TCGA and GEO datasets showed that ECE2 was significantly associated with m6A modification-related genes HNRNPC, IGF2BP1, IGF2BP3 and RBM1.

CONCLUSION

ECE2 is associated with m6A modification and immune infiltration and is a prognostic biomarker in LUAD.

摘要

背景

肺癌的靶向治疗依赖于预后基因,需要进一步研究。目前尚未研究内皮素转换酶 2(ECE2)在肺癌中的作用。

方法

我们分析了来自癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)的肺腺癌(LUAD)和正常相邻组织中 ECE2 的表达及其与临床病理特征的关系。免疫组织化学染色进一步验证了这些发现。使用 R 软件对 ECE2 共表达进行 GO/KEGG 富集分析和基因集富集分析(GSEA)。分析 TIMER、GEPIA 数据库和 TCGA 中的数据,以确定 ECE2 表达与 LUAD 免疫浸润的关系。为了研究 ECE2 表达水平与 LUAD m6A 修饰的关系,分析了 TCGA 数据和 GEO 数据。

结果

ECE2 在包括 LUAD 在内的多种癌症中高表达。ECE2 在区分肿瘤和正常样本方面具有很高的准确性。LUAD 中 ECE2 的表达水平与肿瘤分期和预后显著相关。GO/KEGG 富集分析表明,ECE2 与线粒体基因表达、ATP 酶活性和细胞周期密切相关。GSEA 分析表明,ECE2 相关差异基因富集途径与有丝分裂细胞周期、MYC 途径、PLK1 途径、DNA 甲基化途径、HIF1A 途径和氧化应激诱导的细胞衰老有关。分析 TIMER、GEPIA 数据库和 TCGA 数据集表明,ECE2 表达水平与 B 细胞、CD4+细胞、M2 巨噬细胞、中性粒细胞和树突状细胞呈显著负相关。TCGA 和 GEO 数据集表明,ECE2 与 m6A 修饰相关基因 HNRNPC、IGF2BP1、IGF2BP3 和 RBM1 显著相关。

结论

ECE2 与 m6A 修饰和免疫浸润有关,是 LUAD 的预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad55/9588963/d54b6adc5f47/fendo-13-1013238-g001.jpg

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