Table1_Cuproptosis-Related genes in the prognosis of colorectal cancer and their correlation with the tumor microenvironment.DOC

Colorectal cancer (CRC) is a common tumor disease of the digestive system with high incidence and mortality. Cuproptosis has recently been found to be a new form of cell death. The clinical significance of cuproptosis-related genes (CRGs) in CRC is not clear. In this study, The Cancer Genome Atlas Colon and Rectal Cancer dataset was used to analyze the relationship between CRGs and clinical characteristics of CRC by differential expression analysis and Kaplan–Meier survival (K-M) analysis. Based on CRGs, prognosis model and risk score of CRC was constructed in COADREAD by multivariate Cox analysis. Receiver operating curves (ROC) analysis, K-M analysis and calibration analysis in GDC TCGA Colon Cancer dataset were applied to validating model. Subsequently, the relationship between risk score of CRC and immune microenvironment was analyzed by multiple immune score algorithms. Finally, we found that most CRGs were differentially expressed between tumors and normal tissues. Some CRGs were differentially expressed among different clinical characteristics. K-M analysis showed that the CRGs were related to overall survival (OS), disease-specific survival, and progression-free survival. Subsequently, DLAT and CDKN2A were identified as risk factors for OS in CRC by multivariate Cox analysis, and the risk score was established. K–M analysis showed that there was a significant difference in OS between the high-risk and low-risk groups, which were grouped by risk score median. ROC analysis showed that the risk score performs well in predicting the 1-year, 3-year and 5-year OS. Enrichment analysis showed that the differentially expressed genes between the high- and low-risk groups were enriched in immune-related signaling pathways. Further analysis showed that there were significant differences in the levels of immune cells and stromal cells between the high- and low-risk groups. The high-risk group had higher levels of immune cells and interstitial cells. At the same time, the high-risk group had a higher immune escape ability, and the predicted immune treatment response in the high-risk group was poor. In conclusion, CRGs can be used as prognostic factors in CRC and are closely related to the levels of immune cells and stromal cells in the tumor microenvironment.

结直肠癌（CRC）作为一种消化系统的高发、高死亡率肿瘤疾病，近年来，细胞铜死亡（Cuproptosis）作为一种新的细胞死亡形式被发现。然而，与CRC相关的铜死亡基因（CRGs）在临床上的意义尚不明确。本研究中，通过使用癌症基因组图谱结直肠癌数据集（The Cancer Genome Atlas Colon and Rectal Cancer dataset），运用差异表达分析和Kaplan-Meier生存（K-M）分析，探究了CRGs与CRC临床特征之间的关系。在COADREAD数据库中，基于CRGs构建了CRC的预后模型和风险评分，并通过多变量Cox分析进行验证。在GDC TCGA结直肠癌数据集中，应用接收者操作特征（ROC）曲线分析、K-M分析和校准分析对模型进行验证。随后，通过多种免疫评分算法分析了CRC风险评分与免疫微环境之间的关系。最终，我们发现大多数CRGs在肿瘤组织与正常组织之间存在差异表达。部分CRGs在不同临床特征之间存在差异表达。K-M分析表明，CRGs与总生存期（OS）、疾病特异性生存期和无进展生存期相关。随后，通过多变量Cox分析，DLAT和CDKN2A被确认为CRC的OS风险因素，并建立了风险评分。K-M分析显示，高风险组和低风险组在OS上存在显著差异，且风险评分的中位数被用来分组。ROC分析表明，风险评分在预测1年、3年和5年OS方面表现良好。富集分析显示，高风险组和低风险组之间的差异表达基因富集于免疫相关信号通路。进一步分析表明，高风险组和低风险组在免疫细胞和基质细胞水平上存在显著差异。高风险组具有更高的免疫细胞和间质细胞水平。同时，高风险组具有更高的免疫逃逸能力，并且对高风险组的免疫治疗反应预测较差。综上所述，CRGs可以作为CRC的预后因素，且与肿瘤微环境中免疫细胞和基质细胞水平密切相关。