Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China.
Aging (Albany NY). 2024 May 1;16(9):7774-7798. doi: 10.18632/aging.205782.
Dysregulation of the immune system and N-methyladenosine (m6A) contribute to immune therapy resistance and cancer progression in urothelial carcinoma (UC). This study aims to identify immune-related molecules, that are m6A-modified, and that are associated with tumor progression, poor prognosis, and immunotherapy response.
We identified prognostic immune genes (PIGs) using Cox analysis and random survival forest variable hunting algorithm (RSF-VH) on immune genes retrieved from the Immunology Database and Analysis Portal database (ImmPort). The RM2Target database and MeRIP-seq analysis, combined with a hypergeometric test, assessed m6A methylation in these PIGs. We analyzed the correlation between the immune pattern and prognosis, as well as their association with clinical factors in multiple datasets. Moreover, we explored the interplay between immune patterns, tumor immune cell infiltration, and m6A regulators.
28 PIGs were identified, of which the 10 most significant were termed methylated prognostic immune genes (MPIGs). These MPIGs were used to create an immune pattern score. Kaplan-Meier and Cox analyses indicated this pattern as an independent risk factor for UC. We observed significant associations between the immune pattern, tumor progression, and immune cell infiltration. Differential expression analysis showed correlations with m6A regulators expression. This immune pattern proved effective in predicting immunotherapy response in UC in real-world settings.
The study identified a m6A-modified immune pattern in UC, offering prognostic and therapeutic response predictions. This emphasizes that immune genes may influence tumor immune status and progression through m6A modifications.
免疫系统失调和 N6-甲基腺苷（m6A）的失调导致了膀胱癌（UC）的免疫治疗耐药和癌症进展。本研究旨在鉴定与肿瘤进展、不良预后和免疫治疗反应相关的、受 m6A 修饰的免疫相关分子。
我们使用 COX 分析和随机生存森林变量搜索算法（RSF-VH）从免疫基因数据库（ImmPort）中检索免疫基因，鉴定了预后免疫基因（PIGs）。使用 RM2Target 数据库和 MeRIP-seq 分析，结合超几何检验，评估了这些 PIGs 中的 m6A 甲基化情况。我们分析了免疫模式与预后之间的相关性，以及它们在多个数据集与临床因素之间的相关性。此外，我们还探讨了免疫模式、肿瘤免疫细胞浸润和 m6A 调节剂之间的相互作用。
鉴定出 28 个 PIGs，其中最显著的 10 个被称为甲基化预后免疫基因（MPIGs）。这些 MPIGs 被用来创建一个免疫模式评分。Kaplan-Meier 和 Cox 分析表明，这种模式是 UC 的一个独立危险因素。我们观察到免疫模式与肿瘤进展和免疫细胞浸润之间存在显著关联。差异表达分析显示与 m6A 调节剂表达相关。这种免疫模式在真实世界环境中有效地预测了 UC 的免疫治疗反应。
本研究在 UC 中鉴定出一种受 m6A 修饰的免疫模式，可提供预后和治疗反应预测。这强调了免疫基因可能通过 m6A 修饰影响肿瘤免疫状态和进展。
