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血管生成基因及其相关基因对肺腺癌的预后影响

Prognostic Impact of the Angiogenic Gene and Its Related Genes on Lung Adenocarcinoma.

作者信息

Sun Dongfeng, Gai Zhibo, Wu Jie, Chen Qingfa

机构信息

Department of Thoracic Surgery, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong Medicine and Health Key Laboratory of Emergency Medicine, Shandong Lung Cancer Institute, Shandong Institute of Respiratory Diseases, Jinan, China.

Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.

出版信息

Front Oncol. 2022 Jun 27;12:699824. doi: 10.3389/fonc.2022.699824. eCollection 2022.

DOI:10.3389/fonc.2022.699824
PMID:35832544
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9271775/
Abstract

BACKGROUND

The function of angiogenesis-related genes (ARGs) in lung adenocarcinoma (LUAD) remains poorly documented. This study was designed to reveal ARGs in LUAD and related networks.

METHODS

We worked with sequencing data and clinical information pertaining to LUAD from public databases. ARGs were retrieved from the HALLMARK_ANGIOGENESIS gene set. Differential analysis and Kaplan-Meier (K-M) analysis were performed to authenticate the ARGs associated with LUAD. Weighted gene correlation network analysis was performed on the mining hub genes linked to the abovementioned genes, and functional enrichment analysis was done. Subsequently, Cox regression analyses were used to construct the prognostic gene. and microvessel density were detected using immunohistochemistry.

RESULTS

, an ARG that was highly expressed in patients with LUAD and was closely associated with their weak overall survival was identified. Differentially expressed genes associated with were mainly enriched in entries related to the tubulointerstitial system, immune response, and epithelial cells. A positive correlation was demonstrated between expression and tumor microvessel density in LUAD. Subsequently, a prognostic gene signature was constructed and revealed that 4 genes may predict the survival of LUAD patients. Furthermore, the ESTIMATE and CIBERSORT analyses suggested that our risk scoring system may be implicated in altering the immune microenvironment of patients with LUAD. Finally, a ceRNA network was constructed based on the prognostic genes, and the regulatory networks were examined.

CONCLUSION

, a novel prognostic gene signature associated with ARGs, was constructed for the prognosis of patients with LUAD. This signature may alter the immune microenvironment by modulating the activation of the tubulointerstitial system, epithelial cells, and immune cells, ultimately affecting patient survival.

摘要

背景

血管生成相关基因(ARGs)在肺腺癌(LUAD)中的功能仍鲜有文献记载。本研究旨在揭示LUAD中的ARGs及其相关网络。

方法

我们使用了来自公共数据库的与LUAD相关的测序数据和临床信息。从HALLMARK_ANGIOGENESIS基因集中检索ARGs。进行差异分析和Kaplan-Meier(K-M)分析以验证与LUAD相关的ARGs。对与上述基因相关的挖掘中心基因进行加权基因共表达网络分析,并进行功能富集分析。随后,使用Cox回归分析构建预后基因。并采用免疫组织化学检测微血管密度。

结果

鉴定出一种在LUAD患者中高表达且与其总体生存较差密切相关的ARGs。与该基因相关的差异表达基因主要富集在与肾小管间质系统、免疫反应和上皮细胞相关的条目中。在LUAD中,该基因表达与肿瘤微血管密度之间呈正相关。随后,构建了一个预后基因特征,发现4个基因可预测LUAD患者的生存情况。此外,ESTIMATE和CIBERSORT分析表明,我们的风险评分系统可能与改变LUAD患者免疫微环境有关。最后,基于预后基因构建了ceRNA网络,并对调控网络进行了研究。

结论

构建了一种与ARGs相关的新型预后基因特征,用于LUAD患者的预后评估。该特征可能通过调节肾小管间质系统、上皮细胞和免疫细胞的激活来改变免疫微环境,最终影响患者生存

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