Zhang Moyuan, Cen Tianqi, Huang Shaohui Huang, Wang Chaoyang, Wu Xuan, Zhao Xingru, Xu Zhiwei, Zhang Xiaoju
Xinxiang Medical University, Xinxiang City, 453003, China; Department of Respiratory and Critical Care Medicine, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zheng Zhou City, 450000, China.
Department of Respiratory and Critical Care Medicine, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zheng Zhou City, 450000, China.
Crit Rev Eukaryot Gene Expr. 2025;35(1):49-65. doi: 10.1615/CritRevEukaryotGeneExpr.v34.i1.50.
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.
肺腺癌(LUAD)是全球癌症相关死亡的主要原因,晚期诊断往往导致预后不良。细胞外基质(ECM)在癌细胞进程中起着关键作用。利用来自LUAD的RNA测序大数据,我们旨在筛选与ECM相关的长链非编码RNA(lncRNA),以确定它们的预后意义。我们的研究分析了来自癌症基因组图谱(TCGA)的LUAD队列。单变量Cox分析确定了预后lncRNA,随后进行最小绝对收缩和选择算子(LASSO)回归分析,然后进行多变量Cox分析,以构建预后模型。Kaplan-Meier曲线和ROC曲线评估了该模型的预后性能。创建了一个列线图来预测3年生存率。富集分析确定了该特征所涉及的生物学过程和途径。分析了与肿瘤微环境(TME)和肿瘤突变负担(TMB)的相关性,并预测了LUAD的潜在药物敏感性。我们最初在TCGA LUAD队列中鉴定出218个与ECM相关的基因和427个与ECM相关的lncRNA。随后的单变量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lncRNA。然后,多变量Cox回归分析将这些lncRNA提炼为8个关键lncRNA,形成我们的预后风险特征。列线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。大数据分析建立了一种预后特征,可预测LUAD患者生存和免疫情况,为生存和治疗选择提供了新的见解。