背景：结直肠腺癌（COAD）是一种常见的恶性肿瘤，缺乏有效的预后标志物。铜瘫痪是一种新发现的细胞死亡方式，可能与表观遗传调节因子有关。本研究旨在探索表观遗传调节因子与铜瘫痪的关联，并基于与铜瘫痪相关联的表观遗传调节因子（EACs）建立COAD的预后预测模型。 方法：从TCGA-COAD数据库获取524例COAD患者的RNA测序数据和临床数据，从FerrDb数据库获取与铜瘫痪相关的基因，从GO和EpiFactors等数据库获取表观遗传相关的基因。利用LASSO回归分析和其他方法筛选出与铜瘫痪和预后相关的表观遗传调节因子。计算每个患者的风险评分，将患者分为高风险组和低风险组。然后，比较和分析两组之间的生存差异、功能富集分析、肿瘤突变负荷、化疗药物敏感性和其他指标。 结果：我们发现了与铜瘫痪密切相关的716个表观遗传调节因子，其中35个基因与COAD的预后相关。我们进一步从这35个基因中筛选出了7个EACs来构建预后预测模型。基于这7个基因，计算每个患者的风险评分，并将患者分为高风险组和低风险组。我们发现高风险组的总生存率和无进展生存率明显低于低风险组。该模型在训练集、测试集和整体数据集中显示出良好的预测能力。我们还基于风险评分和其他临床特征构建了预后预测模型，并绘制了相应的图表。此外，我们发现高风险组和低风险组在肿瘤突变负荷、化疗药物敏感性和其他临床方面存在显著差异。 结论：我们基于EACs建立了一种有效的COAD预后预测模型，揭示了表观遗传调节因子与COAD中铜瘫痪的关联。我们希望这个模型不仅能够促进COAD患者的治疗决策，还能推动铜瘫痪领域的研究进展。版权所有 © 2023 刘、王、李、冯、刘和马。

Background: Colorectal adenocarcinoma (COAD) is a common malignant tumor with little effective prognostic markers. Cuproptosis is a newly discovered mode of cell death that may be related to epigenetic regulators. This study aimed to explore the association between epigenetic regulators and cuproptosis, and to establish a prognostic prediction model for COAD based on epigenetic regulators associated with cuproptosis (EACs). Methods: RNA sequencing data and clinical data of 524 COAD patients were obtained from the TCGA-COAD database, cuproptosis-related genes were from the FerrDb database, and epigenetic-related genes were from databases such as GO and EpiFactors. LASSO regression analysis and other methods were used to screen out epigenetic regulators associated with cuproptosis and prognosis. The risk score of each patient was calculated and the patients were divided into high-risk group and low-risk group. Next, the survival difference, functional enrichment analyses, tumor mutation burden, chemotherapy drug sensitivity and other indicators between the two groups were compared and analyzed. Results: We found 716 epigenetic regulators closely related to cuproptosis, among which 35 genes were related to prognosis of COAD. We further screened out 7 EACs from the 35 EACs to construct a prognostic prediction model. We calculated the risk score of each patient based on these 7 genes, and divided the patients into high-risk group and low-risk group. We found that the overall survival rate and progression-free survival rate of the high-risk group were significantly lower than those of the low-risk group. This model showed good predictive ability in the training set, test set and overall data set. We also constructed a prognostic prediction model based on risk score and other clinical features, and drew the corresponding Nomogram. In addition, we found significant differences between the high-risk group and the low-risk group in tumor mutation burden, chemotherapy drug sensitivity and other clinical aspects. Conclusion: We established an effective predictive prediction model for COAD based on EACs, revealing the association between epigenetic regulators and cuproptosis in COAD. We hope that this model can not only facilitate the treatment decision of COAD patients, but also promote the research progress in the field of cuproptosis.Copyright © 2023 Liu, Wang, Li, Feng, Liu and Ma.