Background. In recent years, immune-associated genes (IAGs) have been documented as having critical roles in the occurrence and progression of muscle-invasive bladder cancer (MIBC). Novel immune-related biomarkers and a robust prognostic signature for MIBC patients are still limited. The study is aimed at developing an IAG-based signature to predict the prognosis of MIBC patients. Methods. In the present study, we identified differentially expressed IAGs in MIBC by using transcriptomics data from The Cancer Genome Atlas (TCGA) database and proteomics data from our samples. We further constructed an IAG-based signature and evaluated its prognostic and predictive value by survival analysis and nomogram. Tumor Immune Estimation Resource (TIMER) was applied to explore the correlation between the IAG-based signature and immune cell infiltration in the microenvironment of MIBC. Results. A total of 22 differentially expressed IAGs were identified, and 2 IAGs (NR2F6 and AHNAK) were used to establish a prognostic signature. Subsequently, survival analysis showed that high-risk scores were significantly correlated with poor overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) of MIBC patients. A prognostic nomogram was constructed by integrating clinical factors with the IAG-based signature risk score. In addition, the IAG-based signature risk score was positively associated with the infiltration of macrophages and dendritic cells in MIBC. Conclusions. We constructed and verified a novel IAG-based signature, which could predict the prognosis of MIBC and might reflect the status of the immune microenvironment of MIBC. Further studies in more independent clinical cohorts and further experimental exploration of the prognostic IAG-based signature are still needed.

中文翻译：

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在肌肉浸润性膀胱癌中构建基于免疫相关基因的特征

背景。近年来，免疫相关基因（IAGs）已被证明在肌肉浸润性膀胱癌（MIBC）的发生和进展中起关键作用。MIBC 患者的新型免疫相关生物标志物和强有力的预后特征仍然有限。该研究旨在开发基于 IAG 的特征来预测 MIBC 患者的预后。方法. 在本研究中，我们通过使用癌症基因组图谱 (TCGA) 数据库中的转录组学数据和我们样本中的蛋白质组学数据鉴定了 MIBC 中差异表达的 IAG。我们进一步构建了基于 IAG 的特征，并通过生存分析和列线图评估了其预后和预测价值。应用肿瘤免疫估计资源 (TIMER) 探索基于 IAG 的特征与 MIBC 微环境中免疫细胞浸润之间的相关性。结果。共鉴定出 22 个差异表达的 IAG，其中 2 个 IAG（NR2F6和ANHAK) 用于建立预后特征。随后，生存分析表明，高风险评分与 MIBC 患者较差的总生存期 (OS)、无进展生存期 (PFS) 和无病生存期 (DFS) 显着相关。通过将临床因素与基于 IAG 的特征风险评分相结合来构建预后列线图。此外，基于 IAG 的特征风险评分与 MIBC 中巨噬细胞和树突状细胞的浸润呈正相关。结论. 我们构建并验证了一种新的基于 IAG 的特征，它可以预测 MIBC 的预后，并可能反映 MIBC 的免疫微环境状态。仍然需要在更独立的临床队列中进行进一步的研究，并对基于 IAG 的预后特征进行进一步的实验探索。