Table_1_A novel cuproptosis-related lncRNA signature predicts the prognosis and immune landscape in bladder cancer.xls

BackgroundBladder cancer (BLCA) is one of the deadliest diseases, with over 550,000 new cases and 170,000 deaths globally every year. Cuproptosis is a copper-triggered programmed cell death and is associated with the prognosis and immune response of various cancers. Long non-coding RNA (lncRNA) could serve as a prognostic biomarker and is involved in the progression of BLCA.
MethodsThe gene expression profile of cuproptosis-related lncRNAs was analyzed by using data from The Cancer Genome Atlas. Cox regression analysis and least absolute shrinkage and selection operator analysis were performed to construct a cuproptosis-related lncRNA prognostic signature. The predictive performance of this signature was verified by ROC curves and a nomogram. We also explored the difference in immune-related activity, tumor mutation burden (TMB), tumor immune dysfunction and exclusion (TIDE), and drug sensitivity between the high- and low-risk groups.
ResultsWe successfully constructed a cuproptosis-related lncRNA prognostic signature for BLCA including eight lncRNAs (RNF139-AS1, LINC00996, NR2F2-AS1, AL590428.1, SEC24B-AS1, AC006566.1, UBE2Q1-AS1, and AL021978.1). Multivariate Cox analysis suggested that age, clinical stage, and risk score were the independent risk factors for predicting prognosis of BLCA. Further analysis revealed that this signature not only had higher diagnostic efficiency compared to other clinical features but also had a good performance in predicting the 1-year, 3-year, and 5-year overall survival rate in BLCA. Notably, BLCA patients with a low risk score seemed to be associated with an inflamed tumor immune microenvironment and had a higher TMB level than those with a high risk score. In addition, patients with a high risk score had a higher TIDE score and a higher half maximal inhibitory concentration value of many therapeutic drugs than those with a low risk score.
ConclusionWe identified a novel cuproptosis-related lncRNA signature that could predict the prognosis and immune landscape of BLCA.

背景：膀胱癌（BLCA）是致死性最高的恶性肿瘤之一，每年全球新增病例超55万例，死亡病例达17万例。铜死亡（Cuproptosis）是一种铜诱导的程序性细胞死亡方式，与多种癌症的预后及免疫应答密切相关。长链非编码RNA（long non-coding RNA, lncRNA）可作为预后生物标志物，并参与膀胱癌的进展过程。
方法：本研究采用癌症基因组图谱（The Cancer Genome Atlas, TCGA）的数据，分析铜死亡相关长链非编码RNA的基因表达谱。通过Cox回归分析及最小绝对收缩和选择算子（least absolute shrinkage and selection operator, LASSO）分析，构建铜死亡相关长链非编码RNA预后特征模型。采用受试者工作特征（receiver operating characteristic, ROC）曲线及列线图（nomogram）验证该特征模型的预测性能。此外，本研究还比较了高、低风险组在免疫相关活性、肿瘤突变负荷（tumor mutation burden, TMB）、肿瘤免疫功能异常与排斥（tumor immune dysfunction and exclusion, TIDE）以及药物敏感性方面的差异。
结果：本研究成功构建了包含8个长链非编码RNA的膀胱癌铜死亡相关预后特征模型，涉及的lncRNA分别为RNF139-AS1、LINC00996、NR2F2-AS1、AL590428.1、SEC24B-AS1、AC006566.1、UBE2Q1-AS1及AL021978.1。多因素Cox分析结果显示，年龄、临床分期及风险评分均为膀胱癌预后预测的独立危险因素。进一步分析表明，相较于其他临床特征，该特征模型不仅具备更高的诊断效能，还能有效预测膀胱癌患者1年、3年及5年的总生存率。值得注意的是，低风险评分的膀胱癌患者呈现炎症性肿瘤免疫微环境，且肿瘤突变负荷水平高于高风险评分患者。此外，高风险评分患者的TIDE评分更高，且对多种治疗药物的半抑制浓度（half maximal inhibitory concentration, IC50）均高于低风险评分患者。
结论：本研究鉴定出一种全新的膀胱癌铜死亡相关长链非编码RNA特征模型，可用于预测膀胱癌的预后及免疫微环境状态。