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Research Article

基于血管生成相关lncRNAs的结肠癌预后预测风险评分模型的建立

卷 31, 期 17, 2024

发表于: 13 November, 2023

页: [2449 - 2466] 页: 18

弟呕挨: 10.2174/0109298673277243231108071620

价格: $65

摘要

目标:筛选基于结肠腺癌(COAD)血管生成相关的关键lncRNAs，构建预测COAD预后的RiskScore模型，有助于揭示COAD的发病机制，优化临床治疗。 背景:lncRNAs在肿瘤进展和预后中的调节作用已被证实，但很少有研究探讨血管生成相关的lncRNAs在COAD中的作用。 目的:识别血管生成相关的关键lncRNAs并建立RiskScore模型，预测COAD患者的生存概率，帮助优化临床治疗。 方法:从癌症基因组图谱(TCGA)和基因表达图谱(GEO)数据库中收集样本数据。采用单样本基因集富集分析(ssGSEA)方法计算样品中的HALLMARK通路评分。通过集成管道算法过滤与血管生成相关的lncrna。利用ConsensusClusterPlus对基于lncrna的亚型进行分类，并与其他已建立的亚型进行比较。基于单变量Cox、最小绝对收缩和选择算子(LASSO)回归和逐步回归分析，建立了RiskScore模型。应用R包生存法绘制Kaplan-Meier曲线。用timeROC包绘制随时间变化的ROC曲线。最后，使用肿瘤免疫功能障碍和排斥(TIDE)软件和pRRophetic软件包分析免疫治疗的益处和药物敏感性。结果:通路分析显示血管生成通路是影响COAD患者预后的危险因素。共筛选了66个与血管生成相关的lncRNAs，获得了3个分子亚型(S1、S2、S3)。S1、S2预后好于S3。与现有亚型相比，S3亚型与其他两个亚型差异显著。免疫分析显示S2亚型的免疫细胞评分低于S1和S3亚型，而S1和S3亚型的TIDE评分也最高。我们招募了8个关键的lncRNAs来开发一个RiskScore模型。高风险评分组生存率较低，TIDE评分较高，预计免疫治疗的获益有限，但可能对化疗更敏感。由RiskScore签名和其他临床病理特征设计的nomogram揭示了COAD治疗的合理预测能力。 结论:我们构建了基于血管生成相关lncRNAs的RiskScore模型，该模型可作为COAD患者的潜在预后预测指标，并可为抗血管生成应用的干预提供线索。我们的结果可能有助于评估COAD的预后，并提供更好的治疗策略。

关键词: 结肠腺癌，血管生成相关lncrna, RiskScore模型，预后，药物敏感性，免疫微环境。

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