Department of Urology, Xiangya Hospital, Central South University, Changsha, China.
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
Front Immunol. 2022 Sep 23;13:964393. doi: 10.3389/fimmu.2022.964393. eCollection 2022.
Though immune checkpoint inhibitors (ICIs) exhibit durable efficacy in bladder carcinomas (BLCAs), there are still a large portion of patients insensitive to ICIs treatment.
We systematically evaluated the cuproptosis patterns in BLCA patients based on 46 cuproptosis related genes and correlated these cuproptosis patterns with tumor microenvironment (TME) phenotypes and immunotherapy efficacies. Then, for individual patient's evaluation, we constructed a cuproptosis risk score (CRS) for prognosis and a cuproptosis signature for precise TME phenotypes and immunotherapy efficacies predicting.
Two distinct cuproptosis patterns were generated. These two patterns were consistent with inflamed and noninflamed TME phenotypes and had potential role for predicting immunotherapy efficacies. We constructed a CRS for predicting individual patient's prognosis with high accuracy in TCGA-BLCA. Importantly, this CRS could be well validated in external cohorts including GSE32894 and GSE13507. Then, we developed a cuproptosis signature and found it was significantly negative correlated with tumor-infiltrating lymphocytes (TILs) both in TCGA-BLCA and Xiangya cohorts. Moreover, we revealed that patients in the high cuproptosis signature group represented a noninflamed TME phenotype on the single cell level. As expected, patients in the high cuproptosis signature group showed less sensitive to immunotherapy. Finally, we found that the high and low cuproptosis signature groups were consistent with luminal and basal subtypes of BLCA respectively, which validated the role of signature in TME in terms of molecular subtypes.
Cuproptosis patterns depict different TME phenotypes in BLCA. Our CRS and cuproptosis signature have potential role for predicting prognosis and immunotherapy efficacy, which might guide precise medicine.
尽管免疫检查点抑制剂（ICIs）在膀胱癌（BLCAs）中表现出持久的疗效，但仍有很大一部分患者对 ICI 治疗不敏感。
我们基于 46 个铜死亡相关基因系统地评估了 BLCA 患者的铜死亡模式，并将这些铜死亡模式与肿瘤微环境（TME）表型和免疫治疗疗效相关联。然后，对于个体患者的评估，我们构建了一个用于预后的铜死亡风险评分（CRS）和一个用于精确 TME 表型和免疫治疗疗效预测的铜死亡特征。
生成了两种不同的铜死亡模式。这两种模式与炎症和非炎症 TME 表型一致，具有预测免疫治疗疗效的潜力。我们构建了一个用于预测 TCGA-BLCA 中个体患者预后的 CRS，具有很高的准确性。重要的是，这个 CRS 在包括 GSE32894 和 GSE13507 在内的外部队列中得到了很好的验证。然后，我们开发了一个铜死亡特征，并发现它与 TCGA-BLCA 和湘雅队列中的肿瘤浸润淋巴细胞（TILs）呈显著负相关。此外，我们发现，在单细胞水平上，高铜死亡特征组的患者代表了非炎症 TME 表型。不出所料，高铜死亡特征组的患者对免疫治疗的敏感性较低。最后，我们发现，高和低铜死亡特征组分别与 BLCA 的腔型和基底型一致，这验证了特征在分子亚型方面对 TME 的作用。
铜死亡模式描绘了 BLCA 中不同的 TME 表型。我们的 CRS 和铜死亡特征具有预测预后和免疫治疗疗效的潜力，这可能有助于精准医学。
