Background. Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancers. As cuproptosis, a new cell death mechanism proposed recently, differs from all other known mechanisms regulating cell death, we aimed to create prognostic markers using cuproptosis-related long non-coding ribonucleic acids (RNAs; lncRNAs) and elucidate the molecular mechanism. Methods. Data from transcriptome RNA sequencing of ccRCC samples and the relevant clinical data were downloaded from The Cancer Genome Atlas, and Pearson’s correlation analysis was implemented to obtain the cuproptosis-related lncRNAs. Then, univariate Cox, multivariate Cox, and Least Absolute Shrinkage and Selection Operator Cox analyses were performed to construct the risk signatures. The cuproptosis-related lncRNAs predictive signature was evaluated with receiver operating characteristic curves and subgroup analysis. Finally, Gene Set Enrichment Analysis (GSEA), single-sample GSEA (ssGSEA), tumor immune microenvironment (TIME), and immune checkpoints were performed to explore the relationship between immunity and patient prognosis. Results. Five cuproptosis-related lncRNAs, including FOXD2-AS1, LINC00460, AC091212.1, AC007365.1, and AC026401.3, were used to construct the signature. In the training and test sets, low-risk groups (as identified by a risk score lower than the median) demonstrated a better prognosis with an area under the curve for 1-, 3-, and 5-year survival being 0.793, 0.716, and 0.719, respectively. GSEA analysis suggested significant enrichment of the tricarboxylic acid cycle and metabolism-related pathways in the low-risk group. Besides, both ssGSEA and TIME suggested that the high-risk group exhibited more active immune infiltration. Conclusion. We proposed a cuproptosis-related lncRNAs signature, which had the potential for prognoses and prediction. Our findings might contribute to elucidating potential genomic biomarkers and targets for future therapies in the cuproptosis-related signaling pathways.

中文翻译：

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Cuprotosis 相关 lncRNA 特征可准确预测肾透明细胞癌患者的预后

背景。透明细胞肾细胞癌 (ccRCC) 是最常见的肾癌亚型。由于最近提出的一种新的细胞死亡机制 cuprotosis 不同于所有其他已知的调节细胞死亡的机制，我们旨在使用与 cuprotosis 相关的长链非编码核糖核酸（RNA；lncRNA）创建预后标记并阐明分子机制。方法. 从癌症基因组图谱下载ccRCC样本的转录组RNA测序数据和相关临床数据，并进行Pearson相关分析以获得与铜凋亡相关的lncRNA。然后，进行单变量 Cox、多变量 Cox 和最小绝对收缩和选择操作员 Cox 分析以构建风险特征。使用受试者工作特征曲线和亚组分析评估了与铜凋亡相关的 lncRNA 预测特征。最后，通过基因集富集分析（GSEA）、单样本GSEA（ssGSEA）、肿瘤免疫微环境（TIME）和免疫检查点来探讨免疫与患者预后之间的关系。结果. 五种与铜凋亡相关的 lncRNA，包括 FOXD2-AS1、LINC00460、AC091212.1、AC007365.1 和 AC026401.3，用于构建签名。在训练和测试集中，低风险组（由低于中位数的风险评分确定）表现出更好的预后，1 年、3 年和 5 年生存曲线下面积分别为 0.793、0.716、和 0.719，分别。GSEA 分析表明低风险组中三羧酸循环和代谢相关通路显着富集。此外，ssGSEA 和 TIME 都表明高危人群表现出更活跃的免疫浸润。结论. 我们提出了一种与铜细胞凋亡相关的 lncRNA 特征，它具有预后和预测的潜力。我们的研究结果可能有助于阐明潜在的基因组生物标志物和未来治疗铜细胞凋亡相关信号通路的靶标。