循环肿瘤DNA可以预测可切除胃和胃食管癌患者的复发和存活率
Circulating tumor DNA predicts recurrence and survival in patients with resectable gastric and gastroesophageal junction cancer
影响因子:5.10000
分区:医学2区 / 胃肠肝病学2区 肿瘤学2区
发表日期:2025 Jan
作者:
Cecilie Riis Iden, Salah Mohammad Mustafa, Nadia Øgaard, Tenna Henriksen, Sarah Østrup Jensen, Lise Barlebo Ahlborn, Kristian Egebjerg, Lene Baeksgaard, Rajendra Singh Garbyal, Mette Kjølhede Nedergaard, Michael Patrick Achiam, Claus Lindbjerg Andersen, Morten Mau-Sørensen
摘要
胃和胃食管治疗（GEJ）癌症代表着重大的全球健康挑战，其复发率很高，生存率较差。这项研究研究了循环肿瘤DNA（CTDNA）作为评估可切除胃和GEJ腺癌患者复发风险的生物标志物。在化疗，术前化疗和手术后，在基线，一个化疗周期后和手术后，在基线时收集了系列血浆样品。通过DDPCR测试（Trimeth）评估CTDNA，该测试针对基因C9ORF50，KCNQ5和Clip4.CTDNA分析的胃肠道癌特异性甲基化模式，对来自86名患者的229个血浆样品进行了分析。在基线时，在56％的患者中检测到ctDNA，在一次化疗周期后降至37％，术前化疗后25％，手术切除后15％。一个化学疗法后CTDNA的存在与降低无复发生存率（RFS）（HR = 2.54，95％置信区间（CI）1.33-4.85，P = 0.005）和总生存期（OS）（OS）（OS）（HR = 2.23，95％CI 1.07-4.62，P = 0.0032）。类似地，手术后的CTDNA与RF显着较短（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）。多变量回归分析证实了手术后的CTDNA是独立的预后因素（P <0.001）。CTDNA分析有可能鉴定出较高复发风险的患者，从而为可切除的胃胃和GEJ癌症患者提供个性化治疗策略。需要进一步验证较大的队列和CTDNA指导的干预措施以进行将来的临床用途。
Abstract
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.