PDF(Pubmed)
Abstract：
Urothelial carcinoma of the bladder (UCB) is the most prevalent malignant tumor of the urinary system worldwide, which has a significant recurrence rate despite multiple treatment options available. As a unique and novel copper-dependent programmed cell death mechanism, the comprehensive impact of cuproptosis on the tumor immune microenvironment, clinicopathological characteristics and the prognosis of patients remains largely unclear.
A total of 568 UCB samples were thoroughly examined for cuproptosis patterns using data downloaded from TCGA and GEO, based on 10 cuproptosis-related genes reported previously. Then, the univariate COX regression analysis was performed on the genes that differed across the various patterns. To measure individual cuproptosis pattern, a cuproptosis score system was constructed using a principal component analysis algorithm. To validate the scoring system, immunohistochemical staining was performed on tumor tissues with different pathological grades, and experiments in vitro were conducted about the differentially expressed genes related to prognosis. Finally, the capacity of scoring system to predict the response to immunotherapy was verified by using data from IMvigor 210 cohort.
Four unique cuproptosis clusters and two gene clusters were finally found by the investigation. The clinical features and prognosis of patients, as well as the mRNA transcriptome, pathway enrichment, and immune cell infiltration in TME, varied dramatically between various cuproptosis clusters and gene clusters. To identify individual cuproptosis patterns in UCB patients, we also established a cuproptosis scoring system. After validation with multiple methods, it was indicated that the score system could predict the prognosis of UCB patients and was significantly connected to clinical features such TNM category, tumor grade, molecular type and ultimate survival status. The clinical outcomes of UCB patients were predicted effectively according to the tumor mutation burden in conjunction with the scoring system. Furthermore, we found that the cuproptosis score had a significant correlation with the response to immunotherapy and the sensitivity to chemotherapy.
This study revealed the potential impact of cuproptosis on the UCB tumor immune microenvironment and clinical pathological characteristics. The cuproptosis score system could effectively predict the prognosis of patients and the response to chemotherapy and immunotherapy.
A total of 568 UCB samples were thoroughly examined for cuproptosis patterns using data downloaded from TCGA and GEO, based on 10 cuproptosis-related genes reported previously. Then, the univariate COX regression analysis was performed on the genes that differed across the various patterns. To measure individual cuproptosis pattern, a cuproptosis score system was constructed using a principal component analysis algorithm. To validate the scoring system, immunohistochemical staining was performed on tumor tissues with different pathological grades, and experiments in vitro were conducted about the differentially expressed genes related to prognosis. Finally, the capacity of scoring system to predict the response to immunotherapy was verified by using data from IMvigor 210 cohort.
Four unique cuproptosis clusters and two gene clusters were finally found by the investigation. The clinical features and prognosis of patients, as well as the mRNA transcriptome, pathway enrichment, and immune cell infiltration in TME, varied dramatically between various cuproptosis clusters and gene clusters. To identify individual cuproptosis patterns in UCB patients, we also established a cuproptosis scoring system. After validation with multiple methods, it was indicated that the score system could predict the prognosis of UCB patients and was significantly connected to clinical features such TNM category, tumor grade, molecular type and ultimate survival status. The clinical outcomes of UCB patients were predicted effectively according to the tumor mutation burden in conjunction with the scoring system. Furthermore, we found that the cuproptosis score had a significant correlation with the response to immunotherapy and the sensitivity to chemotherapy.
This study revealed the potential impact of cuproptosis on the UCB tumor immune microenvironment and clinical pathological characteristics. The cuproptosis score system could effectively predict the prognosis of patients and the response to chemotherapy and immunotherapy.
摘要：
■膀胱尿路上皮癌（UCB）是世界范围内最常见的泌尿系统恶性肿瘤，尽管有多种治疗选择，但仍有显着的复发率。作为一种独特而新颖的铜依赖性程序性细胞死亡机制，角化对肿瘤免疫微环境的综合影响,患者的临床病理特征和预后仍不清楚。
■使用从TCGA和GEO下载的数据，对总共568个UCB样品进行了全面检查，基于先前报道的10个与角化相关的基因。然后，对不同模式不同的基因进行单变量COX回归分析.为了测量个体角化模式，使用主成分分析算法构建了角化度评分系统。要验证评分系统，对不同病理分级的肿瘤组织进行免疫组织化学染色,并对与预后相关的差异表达基因进行了体外实验。最后,通过使用IMvigor210队列的数据验证了评分系统预测免疫治疗应答的能力.
■通过调查最终发现了四个独特的角化簇和两个基因簇。患者的临床特点及预后,以及mRNA转录组，途径富集，和TME中的免疫细胞浸润，各种角化簇和基因簇之间的差异很大。为了确定UCB患者的个体角化模式，我们还建立了一个倾斜评分系统。使用多个方法验证后，这表明评分系统可以预测UCB患者的预后，并且与TNM类别等临床特征显着相关，肿瘤分级,分子类型和最终生存状态。根据肿瘤突变负荷结合评分系统有效预测UCB患者的临床结局。此外，我们发现,杯突得分与免疫治疗的反应和化疗的敏感性有显著的相关性.
■这项研究揭示了角化对UCB肿瘤免疫微环境和临床病理特征的潜在影响。骨下垂评分系统可以有效预测患者的预后以及对化疗和免疫治疗的反应。
■使用从TCGA和GEO下载的数据，对总共568个UCB样品进行了全面检查，基于先前报道的10个与角化相关的基因。然后，对不同模式不同的基因进行单变量COX回归分析.为了测量个体角化模式，使用主成分分析算法构建了角化度评分系统。要验证评分系统，对不同病理分级的肿瘤组织进行免疫组织化学染色,并对与预后相关的差异表达基因进行了体外实验。最后,通过使用IMvigor210队列的数据验证了评分系统预测免疫治疗应答的能力.
■通过调查最终发现了四个独特的角化簇和两个基因簇。患者的临床特点及预后,以及mRNA转录组，途径富集，和TME中的免疫细胞浸润，各种角化簇和基因簇之间的差异很大。为了确定UCB患者的个体角化模式，我们还建立了一个倾斜评分系统。使用多个方法验证后，这表明评分系统可以预测UCB患者的预后，并且与TNM类别等临床特征显着相关，肿瘤分级,分子类型和最终生存状态。根据肿瘤突变负荷结合评分系统有效预测UCB患者的临床结局。此外，我们发现,杯突得分与免疫治疗的反应和化疗的敏感性有显著的相关性.
■这项研究揭示了角化对UCB肿瘤免疫微环境和临床病理特征的潜在影响。骨下垂评分系统可以有效预测患者的预后以及对化疗和免疫治疗的反应。
