Published online Mar 15, 2023. doi: 10.4251/wjgo.v15.i3.372
Peer-review started: November 23, 2022
First decision: December 9, 2022
Revised: December 22, 2022
Accepted: February 15, 2023
Article in press: February 15, 2023
Published online: March 15, 2023
Processing time: 111 Days and 14.1 Hours
Over the past few years, research into the pathogenesis of colon cancer has progressed rapidly, and cuproptosis is an emerging mode of cellular apoptosis. Exploring the relationship between colon cancer and cuproptosis benefits in identifying novel biomarkers and even improving the outcome of the disease.
To look at the prognostic relationship between colon cancer and the genes associated with cuproptosis and the immune system in patients. The main purpose was to assess whether reasonable induction of these biomarkers reduces mortality among patients with colon cancers.
Data obtained from The Cancer Genome Atlas and Gene Expression Omnibus and the Genotype-Tissue Expression were used in differential analysis to explore differential expression genes associated with cuproptosis and immune activation. The least absolute shrinkage and selection operator and Cox regression algorithm was applied to build a cuproptosis- and immune-related combination model, and the model was utilized for principal component analysis and survival analysis to observe the survival and prognosis of the patients. A series of statistically meaningful transcriptional analysis results demonstrated an intrinsic relationship between cuproptosis and the micro-environment of colon cancer.
Once prognostic characteristics were obtained, the CDKN2A and DLAT genes related to cuproptosis were strongly linked to colon cancer: The first was a risk factor, whereas the second was a protective factor. The finding of the validation analysis showed that the comprehensive model associated with cuproptosis and immunity was statistically significant. Within the component expressions, the expressions of HSPA1A, CDKN2A, and UCN3 differed markedly. Transcription analysis primarily reflects the differential activation of related immune cells and pathways. Furthermore, genes linked to immune checkpoint inhibitors were expressed differently between the subgroups, which may reveal the mechanism of worse prognosis and the different sensitivities of chemotherapy.
The prognosis of the high-risk group evaluated in the combined model was poorer, and cuproptosis was highly correlated with the prognosis of colon cancer. It is possible that we may be able to improve patients’ prognosis by regulating the gene expression to intervene the risk score.
Core Tip: We comprehensively analyzed the effect of cuproptosis and immunity on the prognosis of colon cancer based on the close association between the three. Scrupulously, a variety of algorithms were applied to analyze and construct a three-gene prognostic model whose efficacy was statistically significant in both the training set and the external validation set. Moreover, in order to provide help for prognosis assessment and personalized treatment of colon cancer, we performed immunoinfiltration analysis and immunocheckpoint inhibitor-related genes expression analysis in different risk groups according to the cuproptosis- and immune-related combination model.