鉴定和验证与铜死亡相关的基因 DKC1 在癌症中的作用，重点是食管癌。

BACKGROUND: Esophageal cancer is a common malignancy of the digestive tract. Despite remarkable advancements in its treatment, the overall prognosis for patients remains poor. Cuproptosis is a form of programmed cell death that affects the malignant progression of tumors. This study aimed to examine the impact of the cuproptosis-associated gene DKC1 on the malignant progression of esophageal cancer. METHODS: Clinical and RNA sequencing data of patients with esophageal cancer were extracted from The Cancer Genome Atlas (TCGA). Univariate Cox regression analysis was used to identify the differentially expressed genes related to cuproptosis that are associated with prognosis. We then validated the difference in the expression of DKC1 between tumor and normal tissues via three-dimensional multiomics difference analysis. Subsequently, we investigated the association between DKC1 expression and the tumor microenvironment by employing the TIMER2.0 algorithm, which was further validated in 96 single-cell datasets obtained from the TISCH database. Additionally, the functional role of DKC1 in pancarcinoma was assessed through GSEA. Furthermore, a comprehensive pancancer survival map was constructed, and the expression of DKC1 was verified in various molecular subtypes. By utilizing the CellMiner, GDSC, and CTRP databases, we successfully established a connection between DKC1 and drug sensitivity. Finally, the involvement of DKC1 in the progression of esophageal cancer was investigated through in vivo and in vitro experiments. RESULTS: In this study, we identified a copper death-related gene, DKC1, in esophageal cancer. Furthermore, we observed varying levels of DKC1 expression across different tumor types. Additionally, we conducted an analysis to determine the correlation between DKC1 expression and clinical features, revealing its association with common cell cycle pathways and multiple metabolic pathways. Notably, high DKC1 expression was found to indicate poor prognosis in patients with various tumors and to influence drug sensitivity. Moreover, our investigation revealed significant associations between DKC1 expression and the expression of molecules involved in immune regulation and infiltration of lymphocyte subtypes. Ultimately, the increased expression of DKC1 in esophageal cancer tissues was verified using clinical tissue samples. Furthermore, DKC1-mediated promotion of esophageal cancer cell proliferation and migration was confirmed through both in vitro and in vivo experiments. Additionally, it is plausible that DKC1 may play a role in the regulation of cuproptosis. CONCLUSION: In this study, we conducted a systematic analysis of DKC1 and its regulatory factors and experimentally validated its excellent diagnostic and prognostic abilities in various cancers. Further research indicated that DKC1 may reshape the tumor microenvironment (TME), highlighting the potential of DKC1-based cancer treatment and its usefulness in predicting the response to chemotherapy.

背景：食管癌是一种常见的消化道恶性肿瘤。尽管在治疗方面取得了显著进展，但患者的总体预后仍然较差。铜死亡是一种影响肿瘤恶性进展的程序性细胞死亡形式。本研究旨在研究铜死亡相关基因 DKC1 对食管癌恶性进展的影响。

方法：从癌症基因组图谱（TCGA）中提取食管癌患者的临床和 RNA 测序数据。使用单因素 Cox 回归分析鉴定与预后相关的与铜死亡相关的差异表达基因。然后通过三维多组学差异分析验证 DKC1 在肿瘤组织和正常组织之间的表达差异。随后，通过 TIMER2.0 算法研究 DKC1 表达与肿瘤微环境之间的关系，该算法在来自 TISCH 数据库的 96 个单细胞数据集进一步得到验证。此外，通过 GSEA 评估 DKC1 在泛癌中的功能作用。此外，构建了一个全面的泛癌生存图谱，并在各种分子亚型中验证了 DKC1 的表达。通过使用 CellMiner、GDSC 和 CTRP 数据库，我们成功建立了 DKC1 与药物敏感性之间的联系。最后，通过体内和体外实验研究了 DKC1 在食管癌进展中的作用。

结果：在本研究中，我们确定了食管癌中的一个铜死亡相关基因 DKC1。此外，我们观察到不同肿瘤类型的 DKC1 表达水平存在差异。此外，我们进行了一项分析，以确定 DKC1 表达与临床特征之间的相关性，结果表明其与常见的细胞周期途径和多种代谢途径相关。值得注意的是，在各种肿瘤患者中，高 DKC1 表达预示着预后不良，并影响药物敏感性。此外，我们的研究还揭示了 DKC1 表达与参与免疫调节和淋巴细胞亚型浸润的分子表达之间的显著相关性。最终，使用临床组织样本验证了食管癌组织中 DKC1 表达的增加。此外，通过体外和体内实验证实了 DKC1 介导的促进食管癌细胞增殖和迁移。此外，DKC1 可能在铜死亡的调节中发挥作用。

结论：在本研究中，我们对 DKC1 及其调节因子进行了系统分析，并通过实验验证了其在各种癌症中的出色诊断和预后能力。进一步的研究表明，DKC1 可能重塑肿瘤微环境（TME），突出了基于 DKC1 的癌症治疗的潜力及其在预测化疗反应中的用途。