Use of four genes in exosomes as biomarkers for the identification of lung adenocarcinoma and lung squamous cell carcinoma.

Use of four genes in exosomes as biomarkers for the identification of lung adenocarcinoma and lung squamous cell carcinoma.
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DOI:
10.3892/ol.2021.12510
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发表时间:
2021-04
期刊:
影响因子:
2.9
通讯作者:
Liu J
Liu J
中科院分区:
医学4区
文献类型:
--
作者:
Cao B;Wang P;Gu L;Liu J

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肺腺癌(LUAD)和肺鳞状细胞癌(LUSC)血液中特异性生物标志物的测定对于选择有效的治疗策略和预测预后至关重要。本研究的目的是分析癌症基因组图谱(TCGA)数据库中LUSC和LUAD的差异表达基因(DEGs)。为了寻找非小细胞肺癌(non-small cell lung cancer, NSCLC)的潜在生物标志物,用于临床诊断,我们采用生物信息学方法分析了LUAD和LUSC两种NSCLC亚型的deg。从LUAD或LUSC患者的血清中分离外泌体,并使用透射电镜、纳米颗粒跟踪分析和western blot分析对其进行鉴定。通过逆转录-定量聚合酶链反应,共选择4种差异外泌体mrna与70例非小细胞肺癌患者的血清样本进行验证。建立受试者工作特征曲线,评价4项deg对LUAD和LUSC患者的临床诊断价值。基于TCGA数据的分析揭示了LUSC和LUAD中的DEGs: LUSC和LUAD患者共有1,619个基因差异表达。通过Gene Ontology和Kyoto Encyclopedia of Genes and genomics enrichment analysis分析的deg显示,炎症相关的信号通路(如补体通路)和多种自身免疫性疾病(如系统性红斑狼疮和哮喘)主要富集在LUAD中。细胞周期、Hippo信号通路、Rap1信号通路和Wnt信号通路是LUSC中富集的主要信号通路。肿瘤蛋白P63 (TP63)、角蛋白5 (KRT5)、CEA细胞粘附分子6 (CEACAM6)和表面活性剂蛋白B (SFTPB)联合检测可提高诊断不同亚型肺癌的特异性和敏感性。因此,外泌体TP63、KRT5、CEACAM6和SFTPB mrna可以作为区分LUSC和LUAD的生物标志物,并可能为其鉴别诊断和治疗提供新的策略。
The determination of biomarkers in the blood specific for lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) is crucial for the selection of effective treatment strategies and the prediction of prognosis. The purpose of the present study was to analyze the differentially expressed genes (DEGs) in LUSC and LUAD from The Cancer Genome Atlas (TCGA) database. In order to identify the potential biomarkers for non-small cell lung cancer (NSCLC) for clinical diagnosis, bioinformatics was used to analyze the DEGs of two subtypes of NSCLC, LUAD and LUSC. Exosomes were isolated from the serum of patients with LUAD or LUSC and identified using transmission electron microscopy, nanoparticle tracking analysis and western blot analysis. A total of four differential exosomal mRNAs were selected for validation with serum samples from 70 patients with NSCLC via reverse transcription-quantitative polymerase chain reaction. Receiver operating characteristic curves were established to evaluate the clinical diagnostic value of four DEGs for patients with LUAD and LUSC. The analysis based on TCGA data revealed the DEGs in LUSC and LUAD: A total of 1,619 genes were differentially expressed in patients with LUSC and LUAD. DEGs analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that inflammation-related signaling pathways, such as complement pathways, and multiple autoimmune diseases, such as systemic lupus erythematosus and asthma were mainly enriched in LUAD. The cell cycle, Hippo signaling pathway, Rap1 signaling pathway and Wnt signaling pathway were the main signaling pathways enriched in LUSC. The combination of tumor protein P63 (TP63), keratin 5 (KRT5), CEA cell adhesion molecule 6 (CEACAM6) and surfactant protein B (SFTPB) improved the specificity and sensitivity in the diagnosis of different lung cancer subtypes. Exosomal TP63, KRT5, CEACAM6 and SFTPB mRNAs can thus be used as biomarkers to differentiate between LUSC and LUAD, and may provide a novel strategy for their differential diagnosis and treatment.
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