The metabolic subtypes of gastric cancer reveal treatment preferences

Abstract Understanding the details of gastric cancer metabolic reprogramming is crucial for improving stratified therapy. By utilizing multi-omics data, we investigated metabolic dysregulation in gastric cancer and identified three distinct metabolic subtypes. These subtypes exhibited different prognoses, molecular subtype distributions, and genomic alterations. The metabolic subtypes displayed varying vulnerabilities to chemotherapy, with the C3 subtype being associated with chemotherapy resistance. The C2 subtype showed a preference for immune checkpoint therapy, while C3 subtype may have a better response to targeted natural killer (NK) cell receptor KLRD1 therapy. We discovered and confirmed the pro-cancer role of secreted SPP1 from macrophages through the SPP1/CD44 axis acting on cancer cells. Collectively, we have discovered that patients with different metabolic subtypes exhibit treatment vulnerabilities to chemotherapy and various immunotherapies.