Wu Zhiwei, Lin Changwei, Zhang Fan, Lu Zhixing, Wang Yaohui, Liu Yang, Zhou Zhijiao, Li Liang, Song Liying
Department of Health Management, The Third Xiangya Hospital, Central South University, Changsha 410013, China.
Department of Gastrointestinal Surgery, The Third Xiangya Hospital of Central South University, Changsha 410013, China.
Cancers (Basel). 2023 Apr 13;15(8):2286. doi: 10.3390/cancers15082286.
Cuproptosis is a new form of copper-dependent programmed cell death commonly occurring within the body. There is emerging evidence indicating that cuproptosis has a significant regulatory function in the onset and progression of cancer. However, it is still unclear how cuproptosis regulates cancer and whether other genes are involved in the regulation. Using the TCGA-COAD dataset of 512 samples, we found that seven of ten cuproptosis markers showed prognostic value in colorectal cancer (CRC) using Kaplan-Meier survival analysis. Furthermore, 31 prognostic cuproptosis-related genes were identified using weighted gene co-expression network analysis and univariate Cox analysis. Subsequently, we constructed a 7-PCRG signature using least absolute shrinkage and selection operator (LASSO)-Cox regression analysis. The risk score predicting survival in patients with CRC was evaluated. Two risk groups were classified based on their risk scores. The two groups revealed a significant difference in immune cells, such as B and T cells. Furthermore, we identified differences in many immune functions and checkpoints, including CD276 and CD28. In vitro experiments showed that a hub cuproptosis-related gene, TIGD1, could significantly regulate cuproptosis in CRC after exposure to elesclomol. This study validated that cuproptosis was closely related to the progression of CRC. Seven new cuproptosis-related genes were identified, and the function of TIGD1 in cuproptosis was preliminarily understood. Since a certain concentration of copper in CRC cells is important, cuproptosis may provide a new target for cancer therapy. This study may provide novel insights into the treatment of CRC.
铜死亡是一种常见于体内的新型铜依赖性程序性细胞死亡形式。越来越多的证据表明，铜死亡在癌症的发生和发展中具有重要的调节功能。然而，铜死亡如何调节癌症以及是否有其他基因参与调节仍不清楚。利用512个样本的TCGA-COAD数据集，我们通过Kaplan-Meier生存分析发现，十个铜死亡标志物中的七个在结直肠癌（CRC）中显示出预后价值。此外，使用加权基因共表达网络分析和单变量Cox分析确定了31个与预后相关的铜死亡基因。随后，我们使用最小绝对收缩和选择算子（LASSO）-Cox回归分析构建了一个7-PCRG特征。评估了预测CRC患者生存的风险评分。根据风险评分将患者分为两个风险组。两组在B细胞和T细胞等免疫细胞方面存在显著差异。此外，我们还发现了许多免疫功能和检查点的差异，包括CD276和CD28。体外实验表明，一个关键的铜死亡相关基因TIGD1在暴露于依沙莫林后可显著调节CRC中的铜死亡。本研究证实铜死亡与CRC的进展密切相关。鉴定了七个新的铜死亡相关基因，并初步了解了TIGD1在铜死亡中的功能。由于CRC细胞中一定浓度的铜很重要，铜死亡可能为癌症治疗提供一个新的靶点。本研究可能为CRC的治疗提供新的见解。
