四种腺嘌呤相关 RNA 修饰写入器介导的分子亚型有助于预测膀胱癌的临床结局和治疗选择。

RATIONALE: RNA modifications, containing m6A, m1A, alternative polyadenylation and adenosine-to-inosine RNA editing, involve in critical cancerous immunity and cancerous processes. However, the functional roles of RNA modification writers in bladder cancer (BLCA) are largely unknown. METHODS: In this study, unsupervised clustering was used to identify novel RNA modification writers -mediated molecular subtypes in BLCA. A corresponding quantitative indicator called WriterScore was developed using univariate Cox and Least absolute shrinkage and selection operator (LASSO) analysis. Then, we systematically analyzed the correlation between RNA modification writer-related clusters (WriterScore) and immunological characteristics, classical molecular subtypes, clinicopathologic features and treatment options in BLCA. Finally, we validated the WriterScore in multiple other external BLCA datasets, clinical sample dataset in Shengjing Hospital and pancancer. RESULTS: Two RNA modification writer-related clusters and three DEGclusters were obtained. These RNA modification writer-related clusters (WriterScore) were strongly associated with immunological characteristics, classical molecular subtypes, clinicopathologic features of BLCA. Moreover, WriterScore can properly predict the clinical outcomes and immunotherapy of BLCA patients. CONCLUSION: Our study systematically investigated the role of RNA modification writers and developed a significant WriterScore to guide several treatment options in BLCA, which might bring some potential benefits for BLCA patients.

背景：RNA 修饰（包含 m6A、m1A、可变多聚腺苷酸化和腺苷到肌苷 RNA 编辑）参与了关键的癌症免疫和癌症过程。然而，RNA 修饰写入器在膀胱癌（BLCA）中的功能作用在很大程度上是未知的。

方法：在这项研究中，使用无监督聚类来鉴定 BLCA 中新型 RNA 修饰写入器介导的分子亚型。使用单变量 Cox 和最小绝对收缩和选择算子（LASSO）分析开发了一个相应的定量指标，称为 WriterScore。然后，我们系统地分析了 RNA 修饰写入器相关簇（WriterScore）与 BLCA 中的免疫特征、经典分子亚型、临床病理特征和治疗选择之间的相关性。最后，我们在多个其他外部 BLCA 数据集、盛景医院和泛癌临床样本数据集中验证了 WriterScore。

结果：获得了两个 RNA 修饰写入器相关簇和三个 DEG 簇。这些 RNA 修饰写入器相关簇（WriterScore）与 BLCA 的免疫特征、经典分子亚型、临床病理特征密切相关。此外，WriterScore 可以正确预测 BLCA 患者的临床结局和免疫治疗。

结论：我们的研究系统地研究了 RNA 修饰写入器的作用，并开发了一个有意义的 WriterScore 来指导 BLCA 的几种治疗选择，这可能为 BLCA 患者带来一些潜在的益处。