Cuproptosis-Related genes in the prognosis of colorectal cancer and their correlation with the tumor microenvironment

Weiqiang Wu; Jingqing Dong; Yang Lv; Dongmin Chang

doi:10.3389/fgene.2022.984158

Cuproptosis-Related genes in the prognosis of colorectal cancer and their correlation with the tumor microenvironment

Front Genet. 2022 Sep 28:13:984158. doi: 10.3389/fgene.2022.984158. eCollection 2022.

Authors

Weiqiang Wu^{1

2}, Jingqing Dong³, Yang Lv², Dongmin Chang¹

Affiliations

¹ Department of Surgical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
² Department of Ophthalmology, The 940th Hospital of Joint Logistics Support Force of Chinese PLA, Lanzhou, China.
³ Department of General Surgery, Guangzhou Red Cross Hospital, Medical College, Jinan University, Guangzhou, China.

Abstract

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.

Keywords: colorectal cancer; cuproptosis; immune; overall survival.