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步,患者的总体预后仍然较差.角化是影响肿瘤恶性进展的程序性细胞死亡的一种形式。本研究旨在探讨凋亡相关基因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。使用单变量Cox回归分析来鉴定与预后相关的与角化相关的差异表达基因。然后,我们通过三维多组学差异分析验证了肿瘤和正常组织之间DKC1表达的差异。随后,我们通过使用TIMER2.0算法研究了DKC1表达与肿瘤微环境之间的关联,在从TISCH数据库获得的96个单细胞数据集中进一步验证。此外,通过GSEA评估DKC1在胰腺癌中的功能作用.此外,构建了全面的癌症生存图,并在各种分子亚型中验证了DKC1的表达。通过利用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:在这项研究中,我们发现了一个铜死亡相关基因,DKC1,在食管癌中。此外,我们观察到不同肿瘤类型的DKC1表达水平不同。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,揭示其与常见细胞周期途径和多种代谢途径的关联。值得注意的是,发现DKC1高表达表明各种肿瘤患者的预后不良,并影响药物敏感性。此外,我们的调查显示,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存在显著关联.最终,使用临床组织样本证实了食管癌组织中DKC1的表达增加.此外,通过体外和体内实验证实了DKC1介导的食管癌细胞增殖和迁移的促进。此外,DKC1可能在调节杯突中发挥作用是合理的。
结论:在这项研究中,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),强调了基于DKC1的癌症治疗的潜力及其在预测化疗反应中的有用性。
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.
CONCLUSIONS: 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.