TIGD1 Function as a Potential Cuproptosis Regulator Following a Novel Cuproptosis-Related Gene Risk Signature in Colorectal Cancer

SIMPLE SUMMARY: This study investigates the role of cuproptosis, a type of programmed cell death that depends on copper, in the progression of colorectal cancer (CRC). Using bioinformatics analysis of a large dataset of CRC patient samples, the authors identified seven cuproptosis markers. From this, they developed a predictive model that can predict the prognosis of CRC patients. The study also shows that the gene TIGD1 is involved in regulating cuproptosis in CRC cells. These findings provide new insights into the role of cuproptosis in cancer and may lead to new therapeutic strategies for treating CRC. ABSTRACT: 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.