循环肿瘤DNA在可切除胃癌及胃食管连接部癌患者中的复发预测与生存分析

Circulating tumor DNA predicts recurrence and survival in patients with resectable gastric and gastroesophageal junction cancer

Gastric Cancer

影响因子:5.1

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

DOI: 10.1007/s10120-024-01556-9

摘要

胃癌及胃食管连接部癌（GEJ）是全球重大公共卫生挑战，具有高复发率和预后不良的特征。本研究探讨循环肿瘤DNA（ctDNA）作为评估可切除胃癌和GEJ腺癌（AC）患者复发风险的生物标志物。我们前瞻性纳入接受术前化疗和手术的可切除胃癌及GEJ腺癌患者。采集基线、化疗一周期后、术前化疗后及手术后血浆标本，采用ddPCR（TriMeth）检测特异性甲基化标记的ctDNA，靶向基因C9orf50、KCNQ5和CLIP4的胃肠癌特异性甲基化模式。共分析229份血浆样本，来自86名患者。基线时，56%的患者检测到ctDNA，经过一周期化疗后降至37%，术前化疗后降至25%，手术后降至15%。化疗一周期后检测到ctDNA与复发无病生存期（RFS）（HR=2.54，95%置信区间（CI）1.33-4.85，p=0.005）及总生存期（OS）（HR=2.23，95%CI 1.07-4.62，p=0.032）显著相关。手术后检测到的ctDNA亦与显著缩短的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。多变量回归分析确认术后ctDNA为独立预后因素（p<0.001）。ctDNA检测有望识别复发风险升高的患者，从而实现个体化治疗策略。未来需在更大队列中验证及结合ctDNA引导的干预措施，以促进其临床应用。

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.