Identification of neutrophil extracellular trap-driven gastric cancer heterogeneity and C5AR1 as a therapeutic target

• A novel NET-based classification system reveals two distinct gastric cancer subtypes with unique clinical, molecular, and immune features, impacting therapy response. • A logistic regression model using 12 feature genes reliably differentiates NET-based clusters, offering a potential diagnostic tool. • C5AR1 is identified as a key driver of gastric cancer growth and metastasis, with knockdown suppressing tumor aggressiveness and inducing ROS accumulation. • The study provides a theoretical basis for anti-NET therapies in gastric cancer, highlighting C5AR1 as a promising therapeutic target.