Prognostic Significance and Immune Environment Analysis Using PANoptosis Molecular Clustering in Gastric Cancer

BACKGROUND Stomach adenocarcinoma (STAD) is a common malignant tumor, known for its poor prognosis and challenges in early detection. PANoptosis, a recently discovered form of cell death, is characterized by the integrated activation of pyroptosis, apoptosis, and/or necroptosis pathways. The connection between PANoptosis and the initiation, progression, and prognosis of gastric cancer remains inadequately investigated. MATERIAL AND METHODS Previous research has identified 19 PANoptosis-related genes (PRGs). Using these genes, we performed an in-depth analysis of gastric cancer to identify differentially expressed genes related to prognosis (PRDEGs). These differentially expressed genes were subsequently identified. We analyzed the risk scores, prognoses, and immune landscapes of the patients. Confirmed PRGs and gene clusters have been linked to cancer initiation and progression, patient survival, and immunity. Risk scores were computed, and patients were categorized into 2 groups on the basis of prognostic characteristics linked to 8 specific genes. To increase the accuracy of predicting patient survival, we developed a nomogram that integrates the risk score with various clinical characteristics. RESULTS The analysis revealed that gastric cancer patients classified into high-risk subgroups experienced reduced survival times and a diminished response to immunotherapy. We also found that risk scores demonstrated correlations with immune cell infiltration, tumor microenvironment characteristics (TME), and cancer stem cell (CSC) levels. The differential expression of GPA33 and APOD between gastric tumor and normal tissues was validated by RT-qPCR and immunohistochemical data from the Human Protein Atlas (HPA). In conclusion, our research indicates that genes linked to PANoptosis may serve as key indicators for evaluating the prognosis and survival rates of patients with gastric cancer. CONCLUSIONS This research has the potential to improve the early detection of gastric cancer and contribute to the development of more effective therapeutic approaches.