Affiliation:
1. Second Affiliated Hospital of Nanchang University
Abstract
Abstract
Background
Understanding the details of gastric cancer metabolic reprogramming is crucial for improving stratified therapy.
Methods
By utilizing multi-omics data, we investigated metabolic dysregulation in gastric cancer and identified three distinct metabolic subtypes.
Results
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.
Conclusions
Collectively, we have discovered that patients with different metabolic subtypes exhibit treatment vulnerabilities to chemotherapy and various immunotherapies.
Publisher
Research Square Platform LLC