胃及胃食管结合部 (GEJ) 癌是一项重大的全球健康挑战，具有高复发率和较差的生存结果。本研究探讨循环肿瘤 DNA (ctDNA) 作为评估可切除胃腺癌和 GEJ 腺癌 (AC) 患者复发风险的生物标志物。前瞻性纳入接受围手术期化疗和手术的可切除胃腺癌和 GEJ AC 患者。在基线、一个化疗周期后、术前化疗后和手术后收集系列血浆样本。 ctDNA 通过 ddPCR 测试 (TriMeth) 进行评估，该测试针对胃肠癌特异性基因 C9orf50、KCNQ5 和 CLIP4 的甲基化模式。对来自 86 名患者的 229 份血浆样本进行了 ctDNA 分析。基线时，56% 的患者检测到 ctDNA，经过一个周期的化疗后，这一比例下降至 37%，术前化疗后下降至 25%，手术切除后下降至 15%。一个化疗周期后 ctDNA 的存在与无复发生存期 (RFS) (HR = 2.54, 95% 置信区间 (CI) 1.33-4.85, p = 0.005) 和总生存期 (OS) (HR = 2.23) 降低相关，95% CI 1.07-4.62，p = 0.032）。同样，手术后 ctDNA 与显着缩短的 RFS（HR = 6.22，95% CI 2.39-16.2，p< 0.001）和 OS（HR = 6.37，95% CI 2.10-19.3，p = 0.001）相关。多变量回归分析证实，术后 ctDNA 是一个独立的预后因素 (p<0.001)。ctDNA 分析有可能识别复发风险较高的患者，从而为可切除的胃癌和 GEJ 癌患者提供个性化治疗策略。未来的临床使用需要在更大的队列和 ctDNA 指导的干预措施中进行进一步验证。© 2024。作者。

Gastric and gastroesophageal junction (GEJ) cancer represents a significant global health challenge, with high recurrence rates and poor survival outcomes. This study investigates circulating tumor DNA (ctDNA) as a biomarker for assessing recurrence risk in patients with resectable gastric and GEJ adenocarcinomas (AC).Patients with resectable gastric and GEJ AC, undergoing perioperative chemotherapy and surgery, were prospectively enrolled. Serial plasma samples were collected at baseline, after one cycle of chemotherapy, after preoperative chemotherapy, and after surgery. ctDNA was assessed by a ddPCR test (TriMeth), which targets the gastrointestinal cancer-specific methylation patterns of the genes C9orf50, KCNQ5, and CLIP4.ctDNA analysis was performed on 229 plasma samples from 86 patients. At baseline, ctDNA was detected in 56% of patients, which decreased to 37% following one cycle of chemotherapy, 25% after preoperative chemotherapy and 15% after surgical resection. The presence of ctDNA after one cycle of chemotherapy was associated with reduced recurrence-free survival (RFS) (HR = 2.54, 95% confidence interval (CI) 1.33-4.85, p = 0.005) and overall survival (OS) (HR = 2.23, 95% CI 1.07-4.62, p = 0.032). Similarly, ctDNA after surgery was associated with significantly shorter RFS (HR = 6.22, 95% CI 2.39-16.2, p < 0.001) and OS (HR = 6.37, 95% CI 2.10-19.3, p = 0.001). Multivariable regression analysis confirmed ctDNA after surgery as an independent prognostic factor (p < 0.001).ctDNA analysis has the potential to identify patients at elevated risk of recurrence, thus providing personalized treatment strategies for patients with resectable gastric and GEJ cancer. Further validation in larger cohorts and ctDNA-guided interventions are needed for future clinical use.© 2024. The Author(s).