Data_Sheet_1_Construction of a cuproptosis-associated lncRNA prognostic signature for bladder cancer and experimental validation of cuproptosis-related lncRNA UBE2Q1-AS1.PDF

IntroductionBladder cancer (BLCA) is the ninth most common malignancy worldwide and the fourth most common cancer in men. Copper levels are significantly altered in patients with thyroid, breast, lung, cervical, ovarian, pancreatic, oral, gastric, bladder, and prostate cancers. Outcomes can be predicted by constructing signatures using lncRNA-related genes associated with outcomes.MethodsWe identified lncRNAs related to outcomes, those differentially expressed in bladder cancer, and cuproptosis-related lncRNAs from TCGA. We identified the intersection to obtain 12 genes and established a prognostic risk signature consisting of eight genes using LASSO-penalized multivariate Cox analysis. We constructed a training set, performed survival analysis on the high-and low-risk groups, and performed validation in the test and full sets. There existed a substantial contrast in the likelihood of survival among the cohorts of high and low risk. An in-depth analysis of the gene mutations associated with tumors was conducted to evaluate the risk of developing cancer. We also performed gene analysis on neoadjuvant chemotherapy. We conducted experimental validation on the key gene UBE2Q1-AS1 in our prognostic signature.ResultsThe risk signature we constructed shows significant differences between the high-risk group and the low-risk group. Univariate survival analysis of the eight genes in our signature showed that each gene distinguished between high- and low-risk groups. Sub-group analysis revealed that our risk score differed significantly in tumor stage, age, and gender. The analysis results of the tumor mutation burden (TMB) showed a significant difference in the TMB between the low- and high-risk groups, which had a direct impact on the outcomes. These findings highlight the importance of TMB as a potential prognostic marker in cancer detection and prevention. We analyzed the immune microenvironment and found significant differences in immune function, validation responses, immunotherapy-related positive markers, and critical steps in the tumor immunity cycle between the high- and low-risk groups. We found that the effect of anti-CTLA4 and PD-1 was higher in the high-risk group than in the low-risk group.Gene analysis of neoadjuvant chemotherapy revealed that the treatment effect in the high-risk group was better than in the low-risk group. The key gene UBE2Q1-AS1 in our prognostic signature can significantly influence the cell viability, migration, and proliferation of cancer cells.DiscussionWe established a signature consisting of eight genes constructed from cuproptosis-related lncRNAs that have potential clinical applications for outcomes prediction, diagnosis, and treatment.

膀胱癌（BLCA）是全球第九大常见恶性肿瘤，在男性中排名第四。在甲状腺、乳腺、肺、子宫颈、卵巢、胰腺、口腔、胃、膀胱和前列腺癌患者中，铜水平发生显著改变。通过构建与预后相关的长链非编码RNA（lncRNA）相关基因的签名，可以预测预后。方法：我们从TCGA数据库中确定了与预后相关的、在膀胱癌中差异表达的lncRNA以及与铜死亡相关的lncRNA。我们确定了交集以获得12个基因，并利用LASSO惩罚多元Cox分析建立了包含八个基因的预后风险签名。我们构建了训练集，对高风险组和低风险组进行了生存分析，并在测试集和全集中进行了验证。高风险组和低风险组在生存概率上存在显著差异。对与肿瘤相关的基因突变进行了深入分析，以评估发生癌症的风险。我们还对新辅助化疗进行了基因分析。我们对预后签名中的关键基因UBE2Q1-AS1进行了实验验证。结果：我们构建的风险签名在高风险组和低风险组之间显示出显著差异。对我们签名中的八个基因进行单变量生存分析表明，每个基因都能区分高风险组和低风险组。亚组分析显示，我们的风险评分在肿瘤分期、年龄和性别方面存在显著差异。肿瘤突变负荷（TMB）的分析结果显示，低风险组和高风险组之间的TMB存在显著差异，这对预后有直接影响。这些发现突出了TMB作为癌症检测和预防中潜在预后标志物的重要性。我们分析了免疫微环境，并发现高风险组和低风险组在免疫功能、验证反应、免疫治疗相关阳性标志物以及肿瘤免疫周期中的关键步骤之间存在显著差异。我们发现，抗CTLA4和PD-1在高风险组中的效果高于低风险组。新辅助化疗的基因分析显示，高风险组的治疗效果优于低风险组。我们预后签名中的关键基因UBE2Q1-AS1可以显著影响癌细胞的细胞活力、迁移和增殖。讨论：我们建立了一个由与铜死亡相关的lncRNA组成的八个基因签名，该签名具有潜在的预后预测、诊断和治疗临床应用价值。