膀胱尿路上皮癌杯状相关lncRNA预后模型的构建及潜在药物的筛选

Xuzhan Ma, Libin Sun
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摘要

客观的本研究旨在分析膀胱尿路上皮癌(BLCA)患者铜中毒相关的长非编码RNA(lncRNA),构建预后模型,并筛选其潜在药物。方法。与BLCA相关的转录组表达、临床和突变负荷数据从癌症基因组图谱数据库下载。使用单变量Cox和Lasso回归分析筛选预后lncRNA,然后将其纳入多因素风险比模型。根据预后模型公式计算每个样本的风险评分,并将患者分为高风险组和低风险组进行生存差异分析。使用临床相关的受试者操作特征(ROC)曲线、C指数主成分分析和临床数据统计来评估该模型的预测能力。风险差异lncRNA在功能上富集。我们计算了高危lncRNA的肿瘤突变负担,以及高危和低危组的生存率和肿瘤免疫功能障碍和排除分析。最后,进行了免疫相关性分析和潜在药物筛选。后果筛选出11个具有独立预后意义的lncRNA构建预后模型。生存分析显示,高风险组和低风险组的生存率存在显著差异。ROC曲线下1年、3年和5年的面积分别为0.711、0.679和0.713。构建的模型中lncRNA高风险组和低风险组之间的区别最为明显。风险差异lncRNA与免疫密切相关。根据IC50值筛选灵敏度高的治疗药物。结论11个铜中毒相关lncRNA可作为BLCA的分子生物标志物和治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Construction of a Cuproptosis-Related lncRNA Prognostic Model for Bladder Urothelial Carcinoma and Screening of Potential Drugs
Objective. This study aimed to analyze the cuproptosis-related long non-coding RNA (lncRNA) in patients with bladder urothelial carcinoma (BLCA), construct a prognostic model, and screen its potential drugs. Methods. The transcriptome expression and clinical and mutation burden data related to BLCA were downloaded from The Cancer Genome Atlas database. The prognostic lncRNAs were screened using univariate Cox and Lasso regression analyses, and then included in the multifactor risk ratio model. The risk score of each sample was calculated based on the prognostic model formula, and the patients were divided into high- and low-risk groups for survival difference analysis. Clinically relevant receiver operating characteristic (ROC) curve, C-index principal component analysis, and clinical data statistics were used to evaluate the predictive power of the model. The risk-differential lncRNAs were functionally enriched. We calculated the tumor mutation burden of risk lncRNAs, and survival and the Tumor Immune Dysfunction and Exclusion analyses for high- and low-risk groups. Finally, immunocorrelation analysis and potential drug screening were performed. Results. Eleven lncRNAs with independent prognostic significance were screened out to construct the prognostic model. Survival analysis showed a significant difference in survival between the high- and low-risk groups. The areas under the ROC curve at 1, 3, and 5 years were 0.711, 0.679, and 0.713, respectively. The discrimination between the lncRNA high- and low-risk groups in the constructed model was the most obvious. The risk-differential lncRNAs were closely related to immunity. The treatment drugs with high sensitivity were screened based on the IC50 value. Conclusion. The 11 cuproptosis-related lncRNAs may serve as molecular biomarkers and therapeutic targets for BLCA.
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