DataSheet2_A Cuproptosis-Related Gene Model For Predicting the Prognosis of Clear Cell Renal Cell Carcinoma.xlsx

Despite advances in its treatment, patients diagnosed with clear cell renal cell carcinoma (ccRCC) have a poor prognosis. The mechanism of cuproptosis has been found to differ from other mechanisms that regulate cell death, including apoptosis, iron poisoning, pyrophosphate poisoning, and necrosis. Cuproptosis is an essential component in the regulation of a wide variety of biological processes, such as cell wall remodeling and oxidative stress responses. However, cuproptosis-related genes’ expression in ccRCC patients and their association with the patient’s prognosis remain ambiguous. Evaluation of The Cancer Genome Atlas (TCGA) identified 11 genes associated with cuproptosis that were differently expressed in ccRCC and nearby nontumor tissue. To construct a multigene prognostic model, the prognostic value of 11 genes was assessed and quantified. A signature was constructed by least absolute shrinkage and selection operator (LASSO) Cox regression analysis, and this signature was used to separate ccRCC patients into different risk clusters, with low-risk patients having a much better prognosis. This five-gene signature, when combined with patients’ clinical characteristics, might serve as one independent predictor of overall survival (OS) in ccRCC patients. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that cuproptosis-related genes were enriched in patients with ccRCC. Then, quantitative real-time PCR (qPCR) was employed to verify these genes’ expression. Generally, research has indicated that cuproptosis-related genes are important in tumor immunity and can predict OS of ccRCC patients.

尽管透明细胞肾细胞癌（clear cell renal cell carcinoma, ccRCC）的治疗已取得进展，但确诊患者的预后仍较差。铜死亡（cuproptosis）的调控机制与凋亡、铁中毒、焦磷酸盐中毒及坏死等其他已知细胞死亡方式均存在差异。铜死亡是调控细胞壁重塑、氧化应激应答等多种生物学过程的关键环节。然而，ccRCC患者体内铜死亡相关基因的表达情况，及其与患者预后的关联仍不明确。研究人员通过分析癌症基因组图谱（The Cancer Genome Atlas, TCGA）数据集，鉴定出11个在ccRCC组织与邻近非肿瘤组织中差异表达的铜死亡相关基因。为构建多基因预后模型，研究人员对这11个基因的预后价值进行了评估与量化。通过最小绝对收缩和选择算子（least absolute shrinkage and selection operator, LASSO）Cox回归分析构建了预后特征标签，以此将ccRCC患者划分为不同风险亚组，其中低风险患者的预后显著更优。该五基因特征标签联合患者临床特征，可作为ccRCC患者总生存期（overall survival, OS）的独立预测因子。基因本体（gene ontology, GO）与京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes, KEGG）富集分析结果显示，ccRCC患者体内的铜死亡相关基因存在显著富集。随后研究通过实时荧光定量PCR（quantitative real-time PCR, qPCR）对上述基因的表达情况进行了验证。综上，本研究表明铜死亡相关基因在肿瘤免疫中发挥重要作用，且可用于预测ccRCC患者的总生存期。