一种新的与铜脂死有关的lncRNAs标志物可以预测膀胱移行细胞癌的预后和免疫状态。
A novel cuproptosis-related lncRNAs signature predicts prognostic and immune of bladder urothelial carcinoma.
发表日期:2023
作者:
Zheng Zhou, Yusong Zhou, Wei Liu, Jing Dai
来源:
Frontiers in Genetics
摘要:
膀胱上皮癌(BLCA)仍然是最常见的泌尿系统肿瘤,并且其预后不佳。Cuproptosis是一种新近发现的涉及肿瘤细胞发展的细胞死亡机制。然而,利用Cuproptosis来预测膀胱上皮癌预后和免疫情况仍然不清楚,本研究旨在验证Cuproptosis相关的长非编码RNA(lncRNA)以评估膀胱上皮癌预后和免疫情况。在我们的研究中,我们首先定义了BLCA中Cuproptosis相关基因(CRGs)的表达,其中10个CRGs上调或下调。然后,我们利用The Cancer Genome Atlas膀胱上皮癌(TCGA-BLCA)的RNA序列数据、BLCA患者的临床特征和突变数据构建了Cuproptosis相关mRNA和长非编码RNA的共表达网络,通过Pearson分析获取长非编码RNA。之后,单变量和多变量Cox分析确定了21个长非编码RNA作为独立的预后因子,并使用这些长非编码RNA构建了一个预后模型。然后,进行了生存分析、主成分分析(PCA)、免疫学分析和肿瘤突变频率比较,以验证构建的模型的准确性,并使用GO和KEGG功能富集分析进一步验证Cuproptosis相关长非编码RNA是否与生物途径相关。结果表明,使用Cuproptosis相关长非编码RNA构建的模型可以有效评估BLCA的预后,并且这些长非编码RNA涉及许多生物途径。最后,我们对在高风险组中高度突变的四个基因(TTN、ARID1A、KDM6A、RB1)进行了免疫浸润、免疫检查点和药物敏感性分析,以评估风险基因与BLCA的免疫关联。总之,本研究构建的基于Cuproptosis的lncRNA标志物在BLCA的预后和免疫评估方面具有一定的评估价值,可以为BLCA的治疗和免疫提供一定的参考。版权所有 © 2023 Zhou,Zhou,Liu和Dai。
Bladder Urothelial Carcinoma (BLCA) remains the most common urinary system tumor, and its prognosis is poor. Cuproptosis is a recently discovered novel cell death involved in the development of tumor cells. However, the use of cuproptosis to predict the prognosis and immunity of Bladder Urothelial Carcinoma remains largely unclear, and this study was designed to verify cuproptosis-related long non-coding RNAs (lncRNAs) to estimate the prognosis and immunity of Bladder Urothelial Carcinoma. In our study, we first defined the expression of cuproptosis-related genes (CRGs) in BLCA, and 10 CRGs were up- or downregulated. We then constructed a co-expression network of cuproptosis-related mRNA and long non-coding RNAs using RNA sequence data from The Cancer Genome Atlas Bladder Urothelial Carcinoma (TCGA-BLCA), clinical features and mutation data from BLCA patients to obtain long non-coding RNAs by Pearson analysis. Afterward, univariate and multivariate COX analysis identified 21 long non-coding RNAs as independent prognostic factors and used these long non-coding RNAs to construct a prognostic model. Then, survival analysis, principal component analysis (PCA), immunoassay, and comparison of tumor mutation frequencies were performed to verify the accuracy of the constructed model, and GO and KEGG functional enrichment analysis was used to verify further whether cuproptosis-related long non-coding RNAs were associated with biological pathways. The results showed that the model constructed with cuproptosis-related long non-coding RNAs could effectively evaluate the prognosis of BLCA, and these long non-coding RNAs were involved in numerous biological pathways. Finally, we performed immune infiltration, immune checkpoint and drug sensitivity analyses on four genes (TTN, ARID1A, KDM6A, RB1) that were highly mutated in the high-risk group to evaluate the immune association of risk genes with BLCA. In conclusion, the cuproptosis-related lncRNA markers constructed in this study have evaluation value for prognosis and immunity in BLCA, which can provide a certain reference for the treatment and immunity of BLCA.Copyright © 2023 Zhou, Zhou, Liu and Dai.