Prognostic analysis of disulfidptosis-based ferroptosis-related genes in gastric cancer

Abstract

Abstract Purpose Gastric cancer is one of the highly prevalent malignant tumours of the digestive tract in China and is highly lethal. Several studies have confirmed that Ferroptosis is closely related to the development of gastric cancer. disulfidptosis is a new type of cell death, which is a rapid death mode caused by disulfide stress induced by excessive cystine accumulation in the cell. Currently there are fewer studies on the discovery of disulfidptosis-related genes and their role in cancer development, and this study was used to explore the prognostic analysis of gastric cancer based on the disulfidptosis-related Ferroptosis genes. Methods The mRNA expression profiles of gastric cancer patients and corresponding clinical information were downloaded from the TCGA public database. Ferroptosis, disulfidptosis related gene ensembles were obtained from FerrDb database and published literature search. Differential expression analysis of genes was done on gastric cancer tissues and paracancerous tissues using the R package to screen out the disulfidptosis-related Ferroptosis-based genes with prognostic value. A prognostic model was constructed using LASSO Cox regression analysis, and the RiskScore of the corresponding genes was calculated, and the patients were classified into high-risk and low-risk groups according to the median value of the RiskScore. The predictive ability of the prognostic model for 1-year, 3-year, and 5-year survival was assessed by ROC curves. Multifactorial independent prognostic analysis was used to analyse the correlation between genes in the predictive model and clinicopathological features. The degree of immune infiltration of DEGs in gastric cancer tissues was analysed by Timer database. Results In the TCGA cohort, disulfidptosis-related Ferroptosis genes were differentially expressed between tumours and adjacent normal tissues. In this study, we constructed relevant prognostic models, including DUSP1, TSC22D3, AKR1C2, HNF4A, HELLS, SLC1A5, and BID, and divided the patients into two populations, high and low risk, according to the score of risk, and the overall survival rate of the high-risk group was significantly lower compared with that of the low-risk group (p < 0.001). In multifactorial Cox regression analysis, the risk score could be used as an independent prognostic factor (p < 0.05). The results of immune infiltration analysis showed that the expression level of each DEGs was significantly correlated with the level of immune cell infiltration in gastric cancer (p<0.05). Conclusion In this study, the disulfidptosis-related Ferroptosis gene prognostic model was constructed and identified as an independent prognostic factor, which provides a reference for the treatment and prognosis of gastric cancer patients.