Abstract
Background
This study investigated colon adenocarcinoma (COAD), one of the most common types of cancer globally. In recent years, a novel cell death pathway, hydrogen sulfide poisoning, has been identified, and targeting disulfide reductase may emerge as a new strategy for cancer treatment. However, the predictive potential of disulfidptosis-related gene (DRGs) in COAD and its characteristics in the tumor immune microenvironment (TIME) remain to be further elucidated.
Methods
This study obtained DRGs transcriptome and mutation data of colorectal cancer samples from the Tissue Cancer Genome Atlas (TCGA) database. Pearson and differential expression correlation analysis were used to identify COAD-related DRGs, and a risk prognosis model for DRGs was constructed using univariate least absolute shrinkage and selection operator (LASSO) and Cox regression analysis. Enrichment analysis was then conducted to explore the potential biological functions and signal transduction of differentially expressed genes associated with the model. The reliability of the model was validated through various statistical analyses such as survival analysis, receiver operating characteristic (ROC) curves, calibration plots, and bar graphs. The relationship between the prognostic model, immune microenvironment, and drug sensitivity was examined. Finally, specimens from COAD patients were extracted from human protein atlas (HPA) database and Yantaishan hospital, and compared with normal tissues to verify the expression level of DRGs.
Results
We have successfully established a risk prognostic model containing 6 DRGs (RPA2, TIMP1, WDR1, POLR3K, KTI12, RTKN). This model performs well in predicting the overall survival of patients with COAD. Validation of this model through Cox analysis and clinical indicators shows considerable potential in predicting the prognosis of patients with COAD. Furthermore, there is a significant correlation between the DRGs prognostic model and tumor microenvironment (TME), immune infiltrating cells, and drug sensitivity (p < 0.05). HPA and experimental results verified that the expression levels of RPA2, TIMP1, POLR3K, KTI12 and RTKN in COAD tumors were higher than those in normal tissues, while the expression levels of WDR1 were opposite (p < 0.01).
Conclusion
This study constructed a risk model and identified 6 DRGs as molecular therapeutic targets for COAD. The prognosis and immune therapeutic response of COAD patients are related to DRGs, and targeted therapy for DRGs may provide a new research direction for the diagnosis and treatment of COAD.