Luo Bixian, Lin Jianwei, Ni Anqi, Cai Wei, Yu Xinbo, Wang Mingliang
Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Institute of Nephrology, Zhejiang University, Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province, Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, Zhejiang, China.
Front Oncol. 2022 Nov 25;12:927028. doi: 10.3389/fonc.2022.927028. eCollection 2022.
The prognosis of colon adenocarcinoma (COAD) needs to be improved. Cuproptosis is a recently discovered cell death caused by intracellular overload of copper ions. There have been no reports about the cuproptosis-related prognostic model in COAD. First, we screened 30 differentially expressed genes (DEGs) from patients with COAD using The Cancer Genome Atlas (TCGA) database. Gene Expression Omnibus (GEO) database was used as a validation set to establish a risk model of five cuproptosis-related genes (CKDN2A, SDHB, CCS, ULK1, and CMC1) by least absolute shrinkage and selection operator (LASSO) Cox regression analysis. In both TCGA and GEO cohorts, we could see that overall survival of COAD patients of the low-risk group was longer. Combined with the clinical characteristics, the risk score was found to be an independent prognostic factor. Furthermore, single-sample Gene Set Enrichment Analysis (ssGSEA) showed that the levels of Th1 and Treg immune cells changed both in TCGA and GEO databases. Finally, clinical samples were used to verify the mRNA and protein levels of five risk-model genes. In conclusion, this model could predict the prognosis of COAD patients, and the mechanism may be related to the changes in immune cells in the tumor microenvironment (TME).
结肠腺癌（COAD）的预后有待改善。铜死亡是最近发现的一种由细胞内铜离子过载引起的细胞死亡。目前尚无关于COAD中与铜死亡相关的预后模型的报道。首先，我们使用癌症基因组图谱（TCGA）数据库从COAD患者中筛选出30个差异表达基因（DEG）。基因表达综合数据库（GEO）被用作验证集，通过最小绝对收缩和选择算子（LASSO）Cox回归分析建立了一个由五个与铜死亡相关基因（CKDN2A、SDHB、CCS、ULK1和CMC1）组成的风险模型。在TCGA和GEO队列中，我们都可以看到低风险组的COAD患者总生存期更长。结合临床特征，发现风险评分是一个独立的预后因素。此外，单样本基因集富集分析（ssGSEA）表明，TCGA和GEO数据库中Th1和Treg免疫细胞水平均发生了变化。最后，使用临床样本验证了五个风险模型基因的mRNA和蛋白质水平。总之，该模型可以预测COAD患者的预后，其机制可能与肿瘤微环境（TME）中免疫细胞的变化有关。
