Wang Xin'an, Xu Chengdang, Ma Junjie, Wang Xiao, Chen Xi
Department of Urology, Tongji Hospital, School of Medicine, Tongji University, 389 Xincun Road, Shanghai, 200065, China.
Department of Urology, The Second Affiliated Hospital of Jiaxing University, 1518 North Huancheng Road, Jiaxing, 314000, Zhejiang, China.
Discov Oncol. 2024 Oct 3;15(1):519. doi: 10.1007/s12672-024-01390-6.
Copper (Cu) is used as a cofactor in all organisms, and yet it can be toxic at high intracellular concentrations, causing cell death. Diethyldithiocarbamate (DDC) is a Cu ionophore that can transport Cu effectively into the cell. Copper-diethyldithiocarbamate (Cu-DDC) can treat prostate cancer (PCa) and may correlate with the cell death process. However, the specific Cu-DDC-related cell death genes in PCa are still unknown. Information about the Cu-DDC-related cell death genes was obtained from a previous study. Concurrently, the RNA expression profiles and clinical data were downloaded from public databases such as GEO, TCGA, and CPGEA. Using data from TCGA database, the logistic and lasso regression models were generated using R software. The influence of these genes in affecting PCa progression and prognosis was analyzed. Finally, the expression of these genes was verified in clinical samples. We found five Cu-DDC-related cell death genes associated with the occurrence of PCa from GSE35988, a gene dataset, namely, CDKN2A, PRC1, CDK1, SOX2, and ZNF365. CDKN2A, PRC1, and CDK1 are known to influence PCa patients' disease-free survival (DFS) status and were overexpressed, whereas SOX2 and ZNF365 were under-expressed in PCa in the different databases. Some of these genes can affect PCa progression. Consistent with the database results, the mRNA and protein expression of CDKN2A, PRC1, and CDK1 was also higher in clinical samples. In conclusion, we identified five hub genes which are important for Cu-DDC-related cell death process that can predict the development of PCa.
铜（Cu）在所有生物中都作为一种辅因子发挥作用，然而在细胞内浓度过高时它可能具有毒性，会导致细胞死亡。二乙基二硫代氨基甲酸盐（DDC）是一种铜离子载体，能够有效地将铜转运到细胞内。二乙基二硫代氨基甲酸铜（Cu-DDC）可以治疗前列腺癌（PCa），并且可能与细胞死亡过程相关。然而，PCa中与Cu-DDC相关的特定细胞死亡基因仍然未知。关于与Cu-DDC相关的细胞死亡基因的信息是从先前的一项研究中获得的。同时，RNA表达谱和临床数据从诸如GEO、TCGA和CPGEA等公共数据库中下载。利用TCGA数据库中的数据，使用R软件生成逻辑回归和套索回归模型。分析了这些基因在影响PCa进展和预后方面的作用。最后，在临床样本中验证了这些基因的表达。我们从基因数据集GSE35988中发现了五个与PCa发生相关的与Cu-DDC相关的细胞死亡基因，即CDKN2A、PRC1、CDK1、SOX2和ZNF365。已知CDKN2A、PRC1和CDK1会影响PCa患者的无病生存（DFS）状态且呈过表达，而在不同数据库中，SOX2和ZNF365在PCa中呈低表达。其中一些基因会影响PCa的进展。与数据库结果一致，临床样本中CDKN2A、PRC1和CDK1的mRNA和蛋白表达也较高。总之，我们确定了五个枢纽基因，它们对于与Cu-DDC相关的细胞死亡过程很重要，能够预测PCa的发展。
