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RAGE 是肺腺癌中免疫浸润和细胞衰老的潜在生物标志物。

RAGE is a potential biomarker implicated in immune infiltrates and cellular senescence in lung adenocarcinoma.

机构信息

Department of Pulmonary and Critical Care Medicine, Ningbo Medical Center Lihuili Hospital, Ningbo, China.

出版信息

J Clin Lab Anal. 2022 May;36(5):e24382. doi: 10.1002/jcla.24382. Epub 2022 Mar 31.

Abstract

BACKGROUND

Receptor for Advanced Glycation End-products (RAGE) is an oncogene abnormally expressed in various cancers. However, the clinical value of RAGE and the biological role of RAGE in lung cancer have not been fully investigated.

METHODS

We compared the RAGE expression using several public databases. The relationship between RAGE expression and clinicopathological variables was assessed. The R software package was used to carry out enrichment analyses of RAGE co-expression and gene set enrichment analysis (GSEA). Additionally, we used the TIMER database to assess the association between immune infiltration and RAGE expression. The correlation between RAGE expression and senescence biomarkers in lung adenocarcinoma was analyzed using the TCGA database.

RESULTS

Our findings indicated that the expression of RAGE was downregulated in lung adenocarcinoma, and down-regulation of RAGE was related to poor overall survival and disease-free survival. Functional enrichment analysis indicated that RAGE co-expression genes were mainly associated with neutrophil activation involved in immune response, neutrophil degranulation, and regulation of leukocyte-mediated immunity. Correlation analysis revealed that RAGE expression was closely related to the purity of the tumor and immune infiltration. GSEA indicated that the RAGE-related differential genes were mainly enriched in senescence-related pathways. Besides, the RAGE expression was significantly associated with senescence-related genes.

CONCLUSION

Down-regulation of RAGE expression was associated with poor prognosis, as well as defective immune infiltration and cellular senescence in lung adenocarcinoma.

摘要

背景

晚期糖基化终产物受体(RAGE)是一种在多种癌症中异常表达的癌基因。然而,RAGE 的临床价值以及其在肺癌中的生物学作用尚未得到充分研究。

方法

我们比较了几个公共数据库中的 RAGE 表达。评估了 RAGE 表达与临床病理变量之间的关系。使用 R 软件包进行 RAGE 共表达的富集分析和基因集富集分析(GSEA)。此外,我们使用 TIMER 数据库评估免疫浸润与 RAGE 表达之间的关联。使用 TCGA 数据库分析 RAGE 表达与肺腺癌衰老生物标志物之间的相关性。

结果

我们的研究结果表明,RAGE 在肺腺癌中表达下调,RAGE 的下调与整体生存率和无病生存率差相关。功能富集分析表明,RAGE 共表达基因主要与涉及免疫反应的中性粒细胞激活、中性粒细胞脱颗粒和白细胞介导的免疫调节有关。相关性分析表明,RAGE 表达与肿瘤纯度和免疫浸润密切相关。GSEA 表明,RAGE 相关差异基因主要富集在衰老相关通路中。此外,RAGE 表达与衰老相关基因显著相关。

结论

RAGE 表达下调与肺腺癌预后不良、免疫浸润缺陷和细胞衰老有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8496/9102728/1c9e01a375c5/JCLA-36-e24382-g005.jpg

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