Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, China National Center for Bioinformation, Chinese Academy of Sciences, Beijing, China.
University of Chinese Academy of Sciences, Beijing, China.
Front Immunol. 2022 Apr 11;13:782982. doi: 10.3389/fimmu.2022.782982. eCollection 2022.
Pyroptosis has profound impacts on tumor cell proliferation, invasion, and metastasis and is of great clinical significance for different cancers. However, the role of pyroptosis in the progression and prognosis of muscle invasive bladder cancer (MIBC) remains poorly characterized. Here, we collected multicenter MIBC data and performed integrated analysis to dissect the role of pyroptosis in MIBC and provide an optimized treatment for this disease. Based on transcriptomic data, we developed a novel prognostic model named the pyroptosis-related gene score (PRGScore), which summarizes immunological features, genomic alterations, and clinical characteristics associated with the pyroptosis phenotype. Samples with high PRGScore showed enhancement in CD8 T cell effector function, antigen processing machinery and immune checkpoint and better response to immunotherapy by programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors, which indicates that PRGScore is a valuable signature in the identification of populations sensitive to immune checkpoint inhibitors. Collectively, our study provides insights into further research targeting pyroptosis and its tumor immune microenvironment (TME) and offers an opportunity to optimize the treatment of MIBC.
细胞焦亡对肿瘤细胞的增殖、侵袭和转移有深远影响，对不同类型的癌症均具有重要的临床意义。然而，细胞焦亡在肌层浸润性膀胱癌（MIBC）进展和预后中的作用仍未被充分描述。在这里，我们收集了多中心 MIBC 数据并进行了综合分析，以剖析细胞焦亡在 MIBC 中的作用，并为这种疾病提供优化的治疗方法。基于转录组数据，我们开发了一种新的预后模型，命名为细胞焦亡相关基因评分（PRGScore），它综合了与细胞焦亡表型相关的免疫特征、基因组改变和临床特征。具有高 PRGScore 的样本显示出 CD8 T 细胞效应功能、抗原处理机制和免疫检查点增强，并且对程序性细胞死亡蛋白 1（PD-1）和程序性细胞死亡配体 1（PD-L1）抑制剂的免疫治疗反应更好，这表明 PRGScore 是识别对免疫检查点抑制剂敏感的人群的一个有价值的特征。总之，我们的研究为针对细胞焦亡及其肿瘤免疫微环境（TME）的进一步研究提供了思路，并为优化 MIBC 的治疗提供了机会。
