Xu Chenyang, Liu Yonghao, Zhang Yuxi, Gao Ling
Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.
Department of Imaging, The First Affiliated Hospital of Soochow University, Suzhou, China.
Front Genet. 2022 Oct 12;13:928105. doi: 10.3389/fgene.2022.928105. eCollection 2022.
Colon adenocarcinoma (COAD) is a common malignant tumor of the digestive tract with poor clinical outcomes. Cuproptosis is a novel cell death mechanism and linked to mitochondrial respiration. However, the role of cuproptosis in colon cancer tumor microenvironment (TME) and immune responses remains unknown. We conducted difference analysis to identify the differential expressed cuproptosis-related genes (CRGs). According to the CRGs, the TCGA-COAD samples were categorized using consensus clustering. The LASSO regression analysis was utilized to develop the cuproptosis-related signature. We then verified the model reliability by Kaplan-Meier, PCA, and ROC analysis. The GES39582 cohort served as the validation set. GO and KEGG functional analyses were conducted to investigate the underlying mechanism. We compared the infiltration levels of immune cells, the expression levels of immune checkpoints, and microsatellite instability (MSI) status between the high- and low-risk groups. Additionally, the relationships between the risk signature and immune cells and cancer stem cell (CSC) were analyzed. Finally, we identified 9 differentially expressed CRGs in COAD. According to the expression of CRGs, the TCGA-COAD samples were separated into two clusters. The 11-gene signature was established by LASSO, and it had excellent predictive power for COAD prognosis. Besides, we used the GSE39582 cohort to validate the prognostic value of the model. GO and KEGG results demonstrated that the survival differences between two risk groups was mainly linked to the extracellular matrix (ECM). Further immune characterization analysis showed the significant differences in the immune cell infiltration and immune responses between two risk groups. Overall, the novel cuproptosis-related signature was able to accurately predict COAD prognosis and played important roles in COAD tumor microenvironment and immune responses.
结肠腺癌（COAD）是一种常见的消化道恶性肿瘤，临床预后较差。铜死亡是一种新的细胞死亡机制，与线粒体呼吸有关。然而，铜死亡在结肠癌肿瘤微环境（TME）和免疫反应中的作用尚不清楚。我们进行差异分析以鉴定差异表达的铜死亡相关基因（CRG）。根据CRG，使用一致性聚类对TCGA-COAD样本进行分类。利用LASSO回归分析建立铜死亡相关特征。然后，我们通过Kaplan-Meier、PCA和ROC分析验证模型的可靠性。GES39582队列用作验证集。进行GO和KEGG功能分析以研究潜在机制。我们比较了高风险组和低风险组之间免疫细胞的浸润水平、免疫检查点的表达水平和微卫星不稳定性（MSI）状态。此外，还分析了风险特征与免疫细胞和癌症干细胞（CSC）之间的关系。最后，我们在COAD中鉴定出9个差异表达的CRG。根据CRG的表达，将TCGA-COAD样本分为两个簇。通过LASSO建立了11基因特征，它对COAD预后具有出色的预测能力。此外，我们使用GSE39582队列验证模型的预后价值。GO和KEGG结果表明，两个风险组之间的生存差异主要与细胞外基质（ECM）有关。进一步的免疫特征分析表明，两个风险组之间在免疫细胞浸润和免疫反应方面存在显著差异。总体而言，新的铜死亡相关特征能够准确预测COAD预后，并在COAD肿瘤微环境和免疫反应中发挥重要作用。
