ECM 受体信号通路生物信息学分析的预后价值以及 LAMB1 作为肺腺癌预后生物标志物的前景。

IF 1.3 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL Medicine Pub Date : 2024-09-20 DOI:10.1097/MD.0000000000039854
Tingjun Liu, Jing Liu, Quangang Chen, Lianlian Wu, Lingzhi Zhang, Dandan Qiao, Zhutao Huang, Tianyuan Lu, Ankang Hu, Jie Wang
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引用次数: 0

摘要

细胞外基质(ECM)是由交联蛋白组成的复杂动态网络,是多细胞生物体的基本组成部分。我们的研究探讨了与 ECM 受体相互作用通路相关的基因对免疫靶向治疗和肺腺癌(LUAD)预后的影响。本研究从 NCBI GEO 获得了 LUAD 芯片数据(GSE68465、GSE31210 和 GSE116959)。此外,还从分子特征数据库中下载了与 ECM 受体相互作用通路相关的基因数据。使用 GEO2R 确定差异表达基因,然后分析其与免疫细胞浸润的相关性。单变量 Cox 回归分析筛选出了与 LUAD 患者生存预后显著相关的 ECM 相关基因。此外,Lasso 回归和多变量 Cox 回归分析有助于构建预后模型。通过风险评分和生存分析对患者进行分层。使用接收者操作特征曲线对预后模型进行评估,并使用单变量和多变量Cox回归分析法对风险评分和预后的相关性进行分析。研究人员选择了一个核心基因进行基因组富集分析和CIBERSORT分析,以分别确定其功能和肿瘤浸润免疫细胞比例。结果显示,LUAD差异表达基因中最丰富的通路主要涉及细胞周期、ECM受体相互作用、蛋白质消化吸收、p53信号通路、补体和凝血级联以及酪氨酸代谢。通过共识聚类,确定了两种与 ECM 相关的亚型。此外,还验证了一个与 ECM 相关的预后模型,该模型可预测 LUAD 的生存率,并与肿瘤免疫微环境相关。交叉分析还筛选出了层粘连蛋白亚基 beta 1(LAMB1),以供进一步研究。LAMB1表达较高的LUAD患者的生存时间比LAMB1表达较低的患者长。基因组富集分析和 CIBERSORT 分析显示,LAMB1 的表达与肿瘤免疫微环境相关。总之,我们构建了一个依赖于 ECM 受体相互作用通路的 LUAD 患者预后模型。筛查出 LAMB1 可成为 LUAD 患者的预后风险因素或 LUAD 治疗的潜在靶点。
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The prognostic value of bioinformatics analysis of ECM receptor signaling pathways and LAMB1 identification as a promising prognostic biomarker of lung adenocarcinoma.

The extracellular matrix (ECM) is a complex and dynamic network of cross-linked proteins and a fundamental building block in multicellular organisms. Our study investigates the impact of genes related to the ECM receptor interaction pathway on immune-targeted therapy and lung adenocarcinoma (LUAD) prognosis. This study obtained LUAD chip data (GSE68465, GSE31210, and GSE116959) from NCBI GEO. Moreover, the gene data associated with the ECM receptor interaction pathway was downloaded from the Molecular Signature Database. Differentially expressed genes were identified using GEO2R, followed by analyzing their correlation with immune cell infiltration. Univariate Cox regression analysis screened out ECM-related genes significantly related to the survival prognosis of LUAD patients. Additionally, Lasso regression and multivariate Cox regression analysis helped construct a prognostic model. Patients were stratified by risk score and survival analyses. The prognostic models were evaluated using receiver operating characteristic curves, and risk scores and prognosis associations were analyzed using univariate and multivariate Cox regression analyses. A core gene was selected for gene set enrichment analysis and CIBERSORT analysis to determine its function and tumor-infiltrating immune cell proportion, respectively. The results revealed that the most abundant pathways among differentially expressed genes in LUAD primarily involved the cell cycle, ECM receptor interaction, protein digestion and absorption, p53 signaling pathway, complement and coagulation cascade, and tyrosine metabolism. Two ECM-associated subtypes were identified by consensus clustering. Besides, an ECM-related prognostic model was validated to predict LUAD survival, and it was associated with the tumor immune microenvironment. Additional cross-analysis screened laminin subunit beta 1 (LAMB1) for further research. The survival time of LUAD patients with elevated LAMB1 expression was longer than those with low LAMB1 expression. Gene set enrichment analysis and CIBERSORT analyses revealed that LAMB1 expression correlated with tumor immune microenvironment. In conclusion, a prognostic model of LUAD patients depending on the ECM receptor interaction pathway was constructed. Screening out LAMB1 can become a prognostic risk factor for LUAD patients or a potential target during LUAD treatment.

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来源期刊
Medicine
Medicine 医学-医学:内科
CiteScore
2.80
自引率
0.00%
发文量
4342
审稿时长
>12 weeks
期刊介绍: Medicine is now a fully open access journal, providing authors with a distinctive new service offering continuous publication of original research across a broad spectrum of medical scientific disciplines and sub-specialties. As an open access title, Medicine will continue to provide authors with an established, trusted platform for the publication of their work. To ensure the ongoing quality of Medicine’s content, the peer-review process will only accept content that is scientifically, technically and ethically sound, and in compliance with standard reporting guidelines.
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