Circulating tumor DNA analysis for prediction of prognosis and molecular insights in patients with resectable gastric cancer: results from a prospective study

Abstract This study aimed to evaluate the prognostic value of plasma circulating tumor DNA (ctDNA) level in patients with resectable gastric cancer (GC). A total of 59 patients were prospectively enrolled, with their ctDNA detected and paired tumor tissue collected at various peri‐operative time points. Patients with higher 1‐month post‐operative ctDNA levels demonstrated shorter overall survival status (hazard ratio [HR] = 5.30, p = 0.0022) and a higher risk of recurrence (HR = 3.85, p = 0.011). The model combining ctDNA with conventional serum tumor markers for GC, including carcinoembryonic antigen, carbohydrate antigen 19‐9, and CA72‐4, shows high predictive effectiveness for GC prognosis with an area under the curve of 0.940 ( p = 0.002), which is higher than net ctDNA and other models without ctDNA. Patients with lower ctDNA levels were more likely to have positive stromal programmed cell death ligand 1 expression ( p = 0.046). Additionally, DCAF4L2 mutation was identified as the crucial gene mutation in ctDNA suggesting poor prognosis of patients with GC. Overall, this study highlights that post‐operative ctDNA can serve as an effective biomarker for prognostic prediction and recurrence surveillance in resectable GC.