分子机制一直是研究者的关注重点，它推动了肿瘤形成。铜病理被定义为铜依赖性细胞生长和增殖，包括其在肿瘤形成和增殖中的主要和次要作用，通过信号通路进行。本研究分析了癌症组织中铜病理相关基因（CAGs）表达的差异，并探讨了它们在免疫调节和肿瘤预后中的作用。从多个数据库获取了11,057例癌症样本的原始数据。进行全癌分析以分析CAG表达、单核苷酸变异、拷贝数变异、甲基化标记和微RNA (miRNA)-信使RNA (mRNA)相互作用基因组标记。利用癌症药物敏感性基因组学和癌症治疗反应门户网站数据库评估对CAGs的药物敏感性和耐药性。使用单样本基因集富集分析（ssGSEA）和免疫细胞数量鉴定器数据库，以ssGSEA得分为标准分析免疫细胞浸润。发现CAG在多种癌症中表达异常。在不同癌症中，单核苷酸变异的频率在1%至54%之间。此外，肿瘤微环境中CAG表达与免疫细胞浸润之间的相关性在不同癌症中变化。ATP7A和ATP7B与16种肿瘤中的巨噬细胞呈负相关，包括乳腺浸润性癌和食管癌，而MT1A和MT2A相反。此外，我们建立了铜病理评分，并证明了它们与患者预后、免疫治疗反应性和疾病进展的强相关性（P < 0.05）的关系。最后，我们通过将基因靶点与现有药物匹配来确定潜在的候选药物。本研究报告了全癌中CAG的基因组表征和临床特征。它有助于澄清CAG和肿瘤形成之间的关系，并可能有助于开发生物标志物和新的治疗剂。Copyright © 2023 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.

The molecular mechanisms driving tumorigenesis have continually been the focus of researchers. Cuproplasia is defined as copper-dependent cell growth and proliferation, including its primary and secondary roles in tumor formation and proliferation through signaling pathways. In this study, we analyzed the differences in the expression of cuproplasia-associated genes (CAGs) in pan-cancerous tissues and investigated their role in immune-regulation and tumor prognostication.Raw data from 11,057 cancer samples were acquired from multiple databases. Pan-cancer analysis was conducted to analyze the CAG expression, single-nucleotide variants, copy number variants, methylation signatures, and genomic signatures of micro RNA (miRNA)-messenger RNA (mRNA) interactions. The Genomics of Drug Sensitivity in Cancer and the Cancer Therapeutics Response Portal databases were used to evaluate drug sensitivity and resistance against CAGs. Using single-sample Gene Set Enrichment Analysis (ssGSEA) and Immune Cell Abundance Identifier database, immune cell infiltration was analyzed with the ssGSEA score as the standard.Aberrantly expressed CAGs were found in multiple cancers. The frequency of single-nucleotide variations in CAGs ranged from 1% to 54% among different cancers. Furthermore, the correlation between CAG expression in the tumor microenvironment and immune cell infiltration varied among different cancers. ATP7A and ATP7B were negatively correlated with macrophages in 16 tumors including breast invasive carcinoma and esophageal carcinoma, while the converse was true for MT1A and MT2A. In addition, we established cuproplasia scores and demonstrated their strong correlation with patient prognosis, immunotherapy responsiveness, and disease progression (P < 0.05). Finally, we identified potential candidate drugs by matching gene targets with existing drugs.This study reports the genomic characterization and clinical features of CAGs in pan-cancers. It helps clarify the relationship between CAGs and tumorigenesis, and may be helpful in the development of biomarkers and new therapeutic agents.Copyright © 2023 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.