文章摘要
基于双硫死亡相关长链非编码RNA的CRC预后风险模型的构建
Construction of a CRC prognostic risk model based on disulfide death associated long non coding RNA
投稿时间:2025-03-15  修订日期:2025-03-15
DOI:
中文关键词: CRC  双硫死亡  预后  预测模型
英文关键词: CRC  Disulfide death  Prognostic  Prediction model
基金项目:海南省卫生健康行业科研项目(21A200160)
作者单位邮编
傅祥炜* 武汉科技大学医学院 430081
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中文摘要:
      目的:本研究旨在构建基于双硫死亡相关长链非编码核糖核酸(DRLncRNAs)的结直肠癌(CRC)预后预测模型,并探索其在预测预后及指导个体化治疗中的应用潜力。方法:本研究数据源于癌症基因组图谱(TCGA)数据库,包含CRC患者的RNA测序数据和详细临床资料。采用共表达网络分析筛选出DRLncRNAs。通过单变量Cox回归分析初步筛选与预后相关的DRLncRNAs,再利用LASSO-Cox回归分析进行变量筛选和降维,最后经多变量Cox回归分析确定构建预后风险模型的关键DRLncRNAs。通过Kaplan-Meier生存曲线分析评估预后风险模型对CRC患者生存情况的预测能力。采用受试者工作特征(ROC)曲线分析模型准确性,采用主成分分析(PCA)评估不同基因表达谱对风险分层的区分能力,采用基因本体(GO)、KEGG富集分析评估高表达和低表达基因集在不同风险分组中的富集情况。结果:成功筛选出5种关键 DRLncRNAs(AC068580.3、AL161729.4、ZEB1 - AS1、AC073896.3 和 SNHG16)。在整体集中,该模型 1年、3年、5年生存预测的曲线下面积(AUC)分别为0.674、0.746、0.727;训练集中,1年、3年、5年生存预测AUC分别为0.669、0.762、0.756;测试集中,1年、3年、5 年生存预测AUC分别为 0.666、0.725、0.697。SNHG16、AC073896.3为保护因子,高表达与较好预后相关;ZEB1 - AS1、AC068580.3、AL161729.4为危险因子,高表达预示预后较差。Kaplan-Meier生存分析结果显示,高、低风险组患者的生存情况差异显著(P<0.05),高风险组总体生存率明显更低(P<0.05)。富集分析结果显示,5个DRLncRNAs相关的磷脂酰肌醇介导的信号传导、线粒体基因表达等生物学过程可能参与CRC的发生、发展并引起不良预后。本研究结果显示,成功建立了以5种DRLncRNAs(AC068580.3、AL161729.4、ZEB1-AS1、AC073896.3和SNHG16)为基础的预后风险模型,这些模型与CRC患者的总体生存状态呈现独立相关性。此外,基于这5个DRLncRNAs构建的预后风险模型能有效预测CRC患者的预后情况。结论:本次研究共筛选出AC068580.3、AL161729.4、ZEB1-AS1、AC073896.3和SNHG16等5个DRLncRNAs与CRC患者的预后有关,基于上述5个DRLncRNAs构建的预后风险模型对CRC患者预后具有较高的评估效能。
英文摘要:
      Objective: This study aims to construct a colorectal cancer (CRC) prognosis prediction model based on disulfide death associated long-chain non coding ribonucleic acids (DRLncRNAs), and to explore its potential application in predicting prognosis and guiding personalized treatment. Method: The data for this study was sourced from the Cancer Genome Atlas (TCGA) database, which includes RNA sequencing data and detailed clinical information of CRC patients. Using co expression network analysis to screen DRLncRNAs. Preliminary screening of DRLncRNAs related to prognosis was conducted through univariate Cox regression analysis, followed by variable screening and dimensionality reduction using LASSO Cox regression analysis. Finally, key DRLncRNAs for constructing a prognostic risk model were identified through multivariate Cox regression analysis. Evaluate the predictive ability of prognostic risk models for survival in CRC patients through Kaplan Meier survival curve analysis. The accuracy of the model was analyzed using receiver operating characteristic (ROC) curves, and the ability of different gene expression profiles to distinguish risk stratification was evaluated using principal component analysis (PCA). Gene ontology (GO) and KEGG enrichment analysis were used to evaluate the enrichment of high and low expression gene sets in different risk groups. Result: Five key DRLncRNAs (AC068580.3, AL161729.4, ZEB1-AS1, AC073896.3, and SNHG16) were successfully screened. In the overall concentration, the area under the curve (AUC) of the model''s 1-year, 3-year, and 5-year survival predictions are 0.674, 0.746, and 0.727, respectively; In the training set, the predicted AUC for 1-year, 3-year, and 5-year survival were 0.669, 0.762, and 0.756, respectively; In the test set, the predicted AUC for 1-year, 3-year, and 5-year survival were 0.666, 0.725, and 0.697, respectively. SNHG16 and AC073896.3 are protective factors, and high expression was associated with better prognosis; ZEB1-AS1, AC068580.3, and AL161729.4 were risk factors, and high expression indicates poor prognosis. The Kaplan Meier survival analysis results showed that there was a significant difference in survival between the high-risk and low-risk groups (P<0.05), and the overall survival rate of the high-risk group was significantly lower (P<0.05). The enrichment analysis results showed that the phosphatidylinositol mediated signal transduction, mitochondrial gene expression, and other biological processes related to 5 DRLncRNAs may be involved in the occurrence, development, and poor prognosis of CRC. The results of this study showed that a prognostic risk model based on five DRLncRNAs (AC068580.3, AL161729.4, ZEB1-AS1, AC073896.3, and SNHG16) was successfully established, which showed independent correlation with the overall survival status of CRC patients. In addition, the prognostic risk model constructed based on these 5 DRLncRNAs can effectively predict the prognosis of CRC patients. Conclusion: This study identified five DRLncRNAs, including AC068580.3, AL161729.4, ZEB1-AS1, AC073896.3, and SNHG16, that are associated with the prognosis of CRC patients. The prognostic risk model constructed based on these five DRLncRNAs has a high evaluation efficiency for the prognosis of CRC patients.
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