BackgroundThe increasing incidence of early-stage T1 gastric cancer (GC) underscores the need for accurate preoperative risk stratification of lymph node metastasis (LNM). Current pathological assessments often misclassify patients, leading to unnecessary radical surgeries. MethodsThrough analysis of transcriptomic data from public databases and T1 GC tissues, we identified a 4-mRNA panel (SDS, TESMIN, NEB, and GRB14). We developed and validated a Risk Stratification Assessment (RSA) model combining this panel with clinical features using surgical specimens (training cohort: n = 218; validation cohort: n = 186), gastroscopic biopsies (n = 122), and liquid biopsies (training cohort: n = 147; validation cohort: n = 168). ResultsThe RSA model demonstrated excellent predictive accuracy for LNM in surgical specimens (training AUC = 0.890, validation AUC = 0.878), gastroscopic biopsies (AUC = 0.928), and liquid biopsies (training AUC = 0.873, validation AUC = 0.852). This model significantly reduced overtreatment rates from 83.9 to 44.1% in tissue specimens and from 84.4 to 56.0% in liquid biopsies. The 4-mRNA panel showed specificity for T1 GC compared to other gastrointestinal cancers (P < 0.001). ConclusionsWe developed and validated a novel liquid biopsy-based RSA model that accurately predicts LNM in T1 GC patients. This non-invasive approach could significantly reduce unnecessary surgical interventions and optimize treatment strategies for high-risk T1 GC patients.