A disulfidptosis-related classification and risk signature identifies immunotherapy biomarkers and predicts prognosis in gastric cancer: An observational study

Abstract

Gastric cancer (GC) is one of the most prevalent types of cancer globally, often detected at advanced stages. However, its prognosis remains poor, necessitating the exploration of new biomarkers. Disulfidptosis, a recently identified form of programmed cell death, has not yet been investigated in relation to GC and its associated mechanisms. We analyzed and identified potential associations between disulfidptosis genes and GC clinical risk using TCGA (The Cancer Genome Atlas)-STAD (stomach adenocarcinoma) as the training set and GSE84433 as the validation set. In addition, we explored the prognostic value and potential biological mechanisms of disulfide genes in GC by consensus clustering, enrichment analysis, mutation histology analysis and immune infiltration analysis. Finally, we constructed a disulfidptosis-related risk signature (DRRS) to assess the association between risk class, survival prognosis, and immune infiltration. By utilizing data from 19 disulfidptosis-related genes, we successfully identified subgroups of C1 and C2 patients through consensus clustering. Notably, the 2 groups exhibited significant variations in terms of survival rates, immune scores, and immune cell infiltration. Subsequently, we developed a DRRS via LASSO (least absolute shrinkage and selection operator) regression analysis, incorporating PRICKLE1, NRP1, APOD, MISP3, and SERPINE1. This scoring system effectively distinguished individuals with high and low risks, as verified with a validation set. These findings strongly indicate a close association between disulfidptosis and the immune microenvironment of GC tumors. Moreover, the DRRS demonstrated commendable predictive capabilities for the survival outcomes of GC patients. In this study, we have identified the association between different subtypes of disulfidptosis and alterations in the GC immunotumour microenvironment. Furthermore, we have developed and verified the accuracy of the DRRS, a valuable tool for predicting survival, biological function, and immune infiltration in patients with GC. These findings contribute to a better comprehension of disulfidptosis and offer potential opportunities for innovative approaches in GC treatment.