一种有效的 N6-甲基腺苷相关长非编码 RNA 预后标志物，用于预测膀胱癌患者的预后。

BACKGROUND: Bladder cancer (BLCA) typically has a poor prognosis due to high relapse and metastasis rates. A growing body of evidence indicates that N6-methyladenosine (m6A) and long non-coding RNAs (lncRNAs) play crucial roles in the progression of BLCA and the treatment response of patients with BLCA. Therefore, we conducted a comprehensive RNA-seq analysis of BLCA using data from The Cancer Genome Atlas (TCGA) to establish an m6A-related lncRNA prognostic signature (m6A-RLPS) for BLCA. METHODS: Consensus clustering analysis was used to investigate clusters of BLCA patients with varying prognoses. The least absolute shrinkage and selection operator Cox regression were used to develop the m6A-RLPS. The ESTIMATE and CIBERSORT algorithms were used to evaluate the immune composition. RESULTS: A total of 745 m6A-related lncRNAs were identified using Pearson correlation analysis (|R| > 0.4, p < 0.001). Fifty-one prognostic m6A-related lncRNAs were screened using univariate Cox regression analysis. Through consensus clustering analysis, patients were divided into two clusters (clusters 1 and 2) with different overall survival rates and tumor stages based on the differential expression of the lncRNAs. Enrichment analysis demonstrated that terms related to tumor biological processes and immune-related activities were increased in patient cluster 2, which was more likely to exhibit low survival rates. Nine m6A-related prognostic lncRNAs were finally determined and subsequently used to construct the m6A-RLPS, which was verified to be an independent predictor of prognosis using univariate and multivariate Cox regression analyses. Further, a nomogram based on age, tumor stage, and the m6A-RLPS was generated and showed high accuracy and reliability with respect to predicting the survival outcomes of BLCA patients. The prognostic signature was found to be strongly correlated to tumor-infiltrating immune cells and immune checkpoint expression. CONCLUSIONS: We established a novel m6A-RLPS with a favorable prognostic value for patients with BLCA. We believe that this prognostic signature can provide new insights into the tumorigenesis of BLCA and predict the treatment response in patients with BLCA.

背景：膀胱癌（BLCA）通常预后较差，因为复发和转移率较高。越来越多的证据表明，N6-甲基腺苷（m6A）和长非编码 RNA（lncRNA）在 BLCA 的进展和 BLCA 患者的治疗反应中发挥着关键作用。因此，我们使用来自癌症基因组图谱（TCGA）的数据对 BLCA 进行了全面的 RNA-seq 分析，以建立 BLCA 的 m6A 相关 lncRNA 预后特征（m6A-RLPS）。

方法：采用共识聚类分析研究预后不同的 BLCA 患者的聚类。采用最小绝对收缩和选择算子 Cox 回归建立 m6A-RLPS。采用 ESTIMATE 和 CIBERSORT 算法评估免疫成分。

结果：通过 Pearson 相关分析（|R|>0.4，p<0.001）鉴定出 745 个 m6A 相关 lncRNA。通过单因素 Cox 回归分析筛选出 51 个预后 m6A 相关 lncRNA。通过共识聚类分析，根据 lncRNA 的差异表达，将患者分为两个具有不同总生存率和肿瘤分期的聚类（聚类 1 和 2）。富集分析表明，患者聚类 2 中与肿瘤生物学过程和免疫相关活动相关的术语增加，患者聚类 2 更有可能表现出低生存率。最终确定了 9 个 m6A 相关预后 lncRNA，并随后用于构建 m6A-RLPS，单因素和多因素 Cox 回归分析验证其为预后的独立预测因子。进一步，基于年龄、肿瘤分期和 m6A-RLPS 生成了一个列线图，该列线图在预测 BLCA 患者的生存结果方面具有较高的准确性和可靠性。该预后特征与肿瘤浸润免疫细胞和免疫检查点表达密切相关。

结论：我们建立了一个新的 m6A-RLPS，对 BLCA 患者具有良好的预后价值。我们认为，该预后特征可为 BLCA 的肿瘤发生提供新的见解，并预测 BLCA 患者的治疗反应。