Identification of a Risk Signature and Immune Cell Infiltration Based on Extracellular Matrix-Related lncRNAs in Lung Adenocarcinoma.

IF 1.5 4区 医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Critical Reviews in Eukaryotic Gene Expression Pub Date : 2025-01-01 DOI:10.1615/CritRevEukaryotGeneExpr.v34.i1.50
Moyuan Zhang, Tianqi Cen, Shaohui Huang Huang, Chaoyang Wang, Xuan Wu, Xingru Zhao, Zhiwei Xu, Xiaoju Zhang
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Abstract

Lung adenocarcinoma (LUAD) is the leading cause of cancer-related deaths globally, with late diagnoses often resulting in poor prognoses. The extracellular matrix (ECM) plays a crucial role in cancer cell processes. Using big data from RNA-seq of LUAD, we aimed to screen ECM-related lncRNAs (long noncoding RNAs) to determine their prognostic significance. Our study analyzed the LUAD cohort from The Cancer Genome Atlas (TCGA). Univariate Cox analysis identified prognostic lncRNAs, and least absolute shrinkage and selection operator (LASSO) regression analysis, followed by multivariate Cox analysis, was used to construct a prognostic model. Kaplan-Meier and ROC curves evaluated the model's prognostic performance. A nomogram was created to predict 3-year survival. Enrichment analysis identified biological processes and pathways involved in the signature. Correlations with the tumor microenvironment (TME) and tumor mutation burden (TMB) were analyzed, and potential drug sensitivities for LUAD were predicted. We initially identified 218 ECM-associated genes and 427 ECM-associated lncRNAs within the TCGA LUAD cohort. Subsequent univariate Cox regression analysis selected 26 lncRNAs with significant prognostic value, and an overall survival (OS)-based LASSO Cox regression model further narrowed this to 14 lncRNAs. Multiple Cox regression analyses then distilled these down to 8 critical lncRNAs forming our prognostic risk signature. Nomograms accurately predicted survival. Finally, several potential therapeutic drugs, including afatinib and crizotinib, were identified. Big data analysis established a prognostic signature that predicts survival and immunization in LUAD patients, providing new insights into survival and treatment options.

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基于细胞外基质相关lncrna的肺腺癌风险信号和免疫细胞浸润的鉴定。
肺腺癌(LUAD)是全球癌症相关死亡的主要原因,诊断晚往往导致预后不良。细胞外基质(ECM)在肿瘤细胞过程中起着至关重要的作用。利用LUAD RNA-seq的大数据,我们旨在筛选ecm相关的lncrna(长链非编码rna),以确定其预后意义。我们的研究分析了来自癌症基因组图谱(TCGA)的LUAD队列。单因素Cox分析确定预后lncrna,然后使用最小绝对收缩和选择算子(LASSO)回归分析,然后使用多因素Cox分析构建预后模型。Kaplan-Meier曲线和ROC曲线评估模型的预后性能。创建了一个nomogram来预测3年的生存率。富集分析确定了参与签名的生物过程和途径。分析其与肿瘤微环境(TME)和肿瘤突变负荷(TMB)的相关性,并预测LUAD的潜在药物敏感性。我们最初在TCGA LUAD队列中鉴定了218个ecm相关基因和427个ecm相关lncrna。随后的单因素Cox回归分析选择了26个具有显著预后价值的lncrna,基于总生存期(OS)的LASSO Cox回归模型进一步将其缩小到14个。多重Cox回归分析然后将这些提取为8个关键lncrna,形成我们的预后风险特征。图准确地预测了生存率。最后,确定了几种潜在的治疗药物,包括阿法替尼和克唑替尼。大数据分析建立了预测LUAD患者生存和免疫的预后特征,为生存和治疗方案提供了新的见解。
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来源期刊
Critical Reviews in Eukaryotic Gene Expression
Critical Reviews in Eukaryotic Gene Expression 生物-生物工程与应用微生物
CiteScore
2.70
自引率
0.00%
发文量
67
审稿时长
1 months
期刊介绍: Critical ReviewsTM in Eukaryotic Gene Expression presents timely concepts and experimental approaches that are contributing to rapid advances in our mechanistic understanding of gene regulation, organization, and structure within the contexts of biological control and the diagnosis/treatment of disease. The journal provides in-depth critical reviews, on well-defined topics of immediate interest, written by recognized specialists in the field. Extensive literature citations provide a comprehensive information resource. Reviews are developed from an historical perspective and suggest directions that can be anticipated. Strengths as well as limitations of methodologies and experimental strategies are considered.
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