Research Article

基于MicroRNA的五基因标记预测胃腺癌预后和免疫治疗

卷 31, 期 17, 2024

发表于: 05 January, 2024

页: [2378 - 2399] 页: 22

弟呕挨: 10.2174/0109298673281631231127051017

价格: $65

摘要

目的:我们旨在对胃腺癌(STAD)的分子亚型进行分类,并建立基于mirna的预后基因标记,以预测其预后和治疗反应。 背景:STAD是一种常见的胃肠道恶性肿瘤,其异质性是影响预后和精准治疗的一大挑战。本研究旨在对STAD的分子亚型进行分类,并基于mirna构建预后基因标记,用于预测STAD的预后和治疗反应。目的:探讨STAD的分子分型及预后模型。 方法:利用来自the Cancer Genome Atlas (TCGA)数据库的RNA- seq和miRNA表达谱,构建STAD特异性miRNA-信使RNA (mRNA)竞争内源性RNA (ceRNA)网络,筛选miRNA相关mRNA。然后使用mirna相关基因确定分子亚型。通过单因素Cox分析和多因素回归分析,在GSE84437 Train数据集上建立了预测模型,并在GSE84437 Test、TCGA、GSE84437和GSE66229数据集上进行了验证。使用免疫治疗数据集来评估风险模型的性能。最后,应用定量逆转录聚合酶链反应(qRT-PCR)验证用于风险评分签名的枢纽基因的表达。 结果:我们构建了包含84个mirna和907个mrna的ceRNA网络,并基于TCGASTAD和GSE84437数据集交集的26个基因确定了2个分子亚型。S2亚型预后较差,肿瘤突变负担较低,免疫评分较高,对免疫治疗反应较低。S1亚型对索拉非尼、乙胺嘧啶、Salubrinal、吉西他滨、长春瑞滨和AKT抑制剂VIII更为敏感。接下来,生成一个五基因签名,并在Test和外部数据集中验证其鲁棒性。该风险模型在免疫治疗数据集中也具有良好的预测性能。 结论:本研究揭示了基于mirna的基因在STAD中的潜在机制,为STAD的分类提供了方向。五基因标记准确地预测预后,并有助于治疗选择。

关键词: 胃腺癌,竞争内源性RNA, MicroRNA,分类,预后,免疫治疗。

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