Ge Xinyu, Wang Kaijing, Zhao Tian, Wang Jinyi, Liu Jie, Sun Zhengliang, Chai Zhengjun, Zhang Wen, Li Chengbao, Xu Yan, Chen Guohan
Department of Thoracic Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
Department of Hepatological Surgery, General Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
Exp Physiol. 2025 Jun 25. doi: 10.1113/EP092310.
Recent studies highlight the important roles of cuproptosis in cancer cells. However, the roles of the cuproptosis-related genes (CRGs) in different cancers are still not fully understood. Comprehensive analysis was performed using open-source bioinformatic platforms to disclose the expression profiles, prognostic significance, genomic and epigenetic characteristics, immune microenvironment, and drug sensitivity of CRGs including FDX1, LIAS, LIPT1, DLD, DLAT, PDHA1, PDHB, SLC31A1, MTF1, GLS, CDKN2A, HSPA4 and ATP7B. The colon cancer samples were further obtained to verify the correlation between CDKN2A expression and immune cell infiltration by fluorescence staining. We demonstrated the expression level, methylation and the copy number variant feature, as well as the prognostic significance of CRGs in pan-cancers. The expression of CRGs, especially PDHB, LITP1, ATP7B, HSPA4 and CDKN2A, was significantly correlated with pathological stages. The genetic alteration of CRGs was explored, and CDKN2A was the most frequently altered gene with alteration rate as high as 17% in 10,953 tumour patients. In addition, we revealed a relationship to the tumour immune microenvironment (TIME) and drug resistance in pan-cancer. Moreover, CDKN2A, which was closely correlated to pan-cancer prognosis, was especially analysed including TIME alteration, genomic heterogeneity and tumour stemness. Fluorescence images of colon cancer from different patients demonstrated a positive correlation between CDKN2A expression and the number of CD45 immune cells. Our research has provided a comprehensive understanding of cuproptosis regulators and revealed potential prognostic biomarkers and therapeutic targets for cancers.
最近的研究突出了铜死亡在癌细胞中的重要作用。然而，铜死亡相关基因（CRGs）在不同癌症中的作用仍未完全明确。利用开源生物信息平台进行综合分析，以揭示包括FDX1、LIAS、LIPT1、DLD、DLAT、PDHA1、PDHB、SLC31A1、MTF1、GLS、CDKN2A、HSPA4和ATP7B在内的CRGs的表达谱、预后意义、基因组和表观遗传特征、免疫微环境及药物敏感性。进一步获取结肠癌样本，通过荧光染色验证CDKN2A表达与免疫细胞浸润之间的相关性。我们展示了CRGs在泛癌中的表达水平、甲基化和拷贝数变异特征以及预后意义。CRGs的表达，尤其是PDHB、LITP1、ATP7B、HSPA4和CDKN2A，与病理分期显著相关。探索了CRGs的基因改变，在10953名肿瘤患者中，CDKN2A是改变最频繁的基因，改变率高达17%。此外，我们揭示了泛癌中与肿瘤免疫微环境（TIME）和耐药性的关系。此外，特别分析了与泛癌预后密切相关的CDKN2A，包括TIME改变、基因组异质性和肿瘤干性。来自不同患者的结肠癌荧光图像显示CDKN2A表达与CD45免疫细胞数量呈正相关。我们的研究全面了解了铜死亡调节因子，并揭示了癌症潜在的预后生物标志物和治疗靶点。
