肾嫌色细胞癌铜死亡相关基因预后模型构建与免疫浸润分析
Construction of Cuproptosis-Related Gene Prognostic Model and Immune Infiltration Analysis in Chromophobe Renal Cell Carcinoma
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摘要:目的 探讨铜死亡相关基因在肾嫌色细胞癌（chromophobe renal cell carcinoma，ChRCC）中的表达特征及其在预后评估和免疫调控中的潜在价值，基于TCGA-KICH单一队列构建铜死亡相关风险评分模型，初步探索其预后分层参考价值。方法 通过分析TCGA-KICH中ChRCC患者的转录组数据和临床信息，筛选铜死亡相关的差异基因，通过通路富集分析明确其潜在生物学功能。采用随机森林和多因素Cox回归模型筛选关键基因，构建预后风险评分模型并绘制列线图。利用CIBERSORT算法评估不同风险组间免疫细胞浸润差异，并分析关键铜死亡基因与免疫检查点表达之间的相关性。结果 筛选出SLC31A1、DLAT、PDHA1、DLD、ATP7A、CDKN2A、GLS和LIPT1等铜死亡相关基因，主要富集于三羧酸（tricarboxylic acid，TCA）循环、脂肪酸代谢等通路。基于ATP7A、GLS和LIPT1三个核心基因构建了预后风险评分模型，该模型在内部队列中显示一定区分能力。免疫分析显示，不同风险组间部分免疫细胞浸润比例存在差异，关键基因表达与程序性死亡配体-1（programmed death-ligand 1，PD-L1）免疫检查点呈负相关性，表明铜死亡通路可能与肿瘤免疫微环境变化存在潜在关联。结论 铜死亡关键基因在ChRCC中呈现特征性的差异表达模式（ATP7A显著上调，GLS和LIPT1显著下调）。基于上述基因构建的风险评分模型在本队列中显示出一定的预后评估潜力，可为ChRCC患者风险分层研究提供初步参考，但其准确性仍需在未来大规模队列中进一步验证。Abstract:Objective To investigate the expression characteristics of cuproptosis-related genes in chromophobe renal cell carcinoma (ChRCC) and their potential value in prognostic assessment and immune regulation, to construct a cuproptosis-related risk score model based on the single TCGA-KICH cohort, and to preliminarily explore its reference value in prognostic stratification.Methods Transcriptomic data and clinical information of ChRCC patients in the TCGA-KICH cohort were analyzed to screen cuproptosis-related differentially expressed genes, and pathway enrichment analysis was performed to clarify their potential biological functions. Random forest and multivariate Cox regression analyses were used to identify key genes, construct a prognostic risk score model, and develop a nomogram. CIBERSORT was used to evaluate differences in immune cell infiltration between different risk groups, and correlations between key cuproptosis-related genes and immune checkpoint expression were analyzed.Results Cuproptosis-related genes, including SLC31A1, DLAT, PDHA1, DLD, ATP7A, CDKN2A, GLS, and LIPT1, were identified and were mainly enriched in pathways such as the tricarboxylic acid (TCA) cycle and fatty acid metabolism. A prognostic risk score model was constructed based on the three core genes ATP7A, GLS, and LIPT1, and the model showed a certain discriminatory ability in the internal cohort. Immune analysis showed that the proportions of some immune cell infiltrates differed between risk groups, and the expression of key genes was negatively correlated with the immune checkpoint programmed death-ligand 1 (PD-L1), indicating that the cuproptosis pathway may be potentially associated with changes in the tumor immune microenvironment.Conclusion Key cuproptosis-related genes showed characteristic differential expression patterns in ChRCC, with ATP7A significantly upregulated and GLS and LIPT1 significantly downregulated. The risk score model constructed based on these genes showed a certain potential for prognostic assessment in this cohort and may provide preliminary reference for risk stratification research in ChRCC patients, but its accuracy still requires further validation in future large-scale cohorts.
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