Shen Junlin, Du Mingyang, Liang Shuang, Wang Linhui, Bi Jianbin
Department of Urology, The First Hospital of China Medical University, Shenyang, Liaoning, China.
Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
Front Med (Lausanne). 2023 Aug 8;10:1222543. doi: 10.3389/fmed.2023.1222543. eCollection 2023.
Bladder 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.
We 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.
The 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.
We 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，是男性第四大常见癌症。甲状腺癌、乳腺癌、肺癌、宫颈癌、卵巢癌、胰腺癌、口腔癌、胃癌、膀胱癌和前列腺癌患者体内的铜水平会发生显著变化。通过使用与预后相关的lncRNA相关基因构建特征，可以预测预后。
我们从TCGA中鉴定出与预后相关的lncRNA、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，并使用LASSO惩罚多变量Cox分析建立了一个由8个基因组成的预后风险特征。我们构建了一个训练集，对高风险组和低风险组进行生存分析，并在测试集和全集中进行验证。高风险组和低风险组的生存可能性存在显著差异。对与肿瘤相关的基因突变进行了深入分析，以评估患癌风险。我们还对新辅助化疗进行了基因分析。我们对预后特征中的关键基因UBE2Q1-AS1进行了实验验证。
我们构建的风险特征在高风险组和低风险组之间显示出显著差异。对我们特征中的8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）的分析结果表明，低风险组和高风险组的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，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循环的关键步骤方面存在显著差异。我们发现，高风险组中抗CTLA4和PD-1的效果高于低风险组。新辅助化疗的基因分析表明，高风险组的治疗效果优于低风险组。我们预后特征中的关键基因UBE2Q1-AS1可以显著影响癌细胞的细胞活力、迁移和增殖。
我们建立了一个由8个基因组成的特征，这些基因由与铜死亡相关的lncRNA构建而成，对预后预测、诊断和治疗具有潜在的临床应用价值。
