Raunkilde Louise, Andersen Rikke Fredslund, Thomsen Caroline Brenner, Hansen Torben Frøstrup, Jensen Lars Henrik
Department of Oncology, Vejle Hospital, University Hospital of Southern Denmark, Beriderbakken 4, 7100, Vejle, Denmark; Danish Colorectal Cancer Center South, Vejle Hospital, Beriderbakken 4, 7100, Vejle, Denmark; Department of Regional Health Research, University of Southern Denmark, Campusvej 55, 5230, Odense M, Denmark.
Department of Oncology, Vejle Hospital, University Hospital of Southern Denmark, Beriderbakken 4, 7100, Vejle, Denmark; Danish Colorectal Cancer Center South, Vejle Hospital, Beriderbakken 4, 7100, Vejle, Denmark; Department of Clinical Biochemistry and Immunology, Vejle Hospital, University Hospital of Southern Denmark, Beriderbakken 4, 7100, Vejle, Denmark.
Eur J Surg Oncol. 2025 May;51(5):109586. doi: 10.1016/j.ejso.2025.109586. Epub 2025 Jan 6.
Decision regarding local treatment of colorectal liver metastases (CRLM) is a multidisciplinary assessment, and liver intervention should be performed when the metastases are deemed resectable. There is no standard biomarker to aid neither this decision nor the postoperative treatment decisions. The present prospective, observational study aimed to investigate the potential clinical utility of a combined tumor-specific and organ-specific methylated circulating DNA assay in the perioperative setting of CRLM.
The study included 56 cases with CRLM. Blood samples were drawn preoperatively and postoperatively. Multiplex methylation analysis of the markers NPY, KANK1, and GAL3ST3 (meth-ctDNA) was performed using droplet digital PCR.
The assay detected preoperative and postoperative meth-ctDNA in 37 % and 46 % of patients, respectively. Patients with negative preoperative meth-ctDNA had a longer median PFS compared to those with positive preoperative meth-ctDNA (HR = 2.2, 95 % CI 1.2-3.9, p < 0.01). In a multivariate analysis, preoperative negative meth-ctDNA was identified as a strong independent predictor of PFS (HR = 3.3, 95 % CI 1.5-7.2, p < 0.01). Similarly, patients with negative postoperative meth-ctDNA had longer median PFS (HR = 3.0, 95 % CI = 1.6-5.6, p < 0.001) and OS (HR = 4.1, 95 % CI 1.9-9.1, p < 0.001) compared to those with positive postoperative meth-ctDNA.
Preoperative meth-ctDNA may serve as an important biomarker to inform the multidisciplinary assessment and treatment planning of CRLM. Negative meth-ctDNA may indicate the optimal timing for liver intervention, whereas positive meth-ctDNA may indicate initiation or re-orientation of chemotherapy, or immediate local intervention. Our results confirm postoperative negative meth-ctDNA as a strong prognostic marker of survival.
结直肠癌肝转移（CRLM）局部治疗的决策是一项多学科评估，当转移灶被认为可切除时应进行肝脏干预。目前尚无标准生物标志物可辅助这一决策及术后治疗决策。本前瞻性观察性研究旨在探讨肿瘤特异性和器官特异性甲基化循环DNA联合检测在CRLM围手术期的潜在临床应用价值。
本研究纳入56例CRLM患者。术前和术后采集血样。使用液滴数字PCR对NPY、KANK1和GAL3ST3标记物（甲基化循环肿瘤DNA）进行多重甲基化分析。
该检测分别在37%和46%的患者中检测到术前和术后甲基化循环肿瘤DNA。术前甲基化循环肿瘤DNA阴性的患者中位无进展生存期长于术前甲基化循环肿瘤DNA阳性的患者（风险比=2.2，95%置信区间1.2 - 3.9，p<0.01）。在多变量分析中，术前甲基化循环肿瘤DNA阴性被确定为无进展生存期的强独立预测因子（风险比=3.3，95%置信区间1.5 - 7.2，p<0.01）。同样，术后甲基化循环肿瘤DNA阴性的患者中位无进展生存期（风险比=3.0，95%置信区间=1.6 - 5.6，p<0.001）和总生存期（风险比=4.1，95%置信区间1.9 - 9.1，p<0.001）长于术后甲基化循环肿瘤DNA阳性的患者。
术前甲基化循环肿瘤DNA可作为重要生物标志物，为CRLM的多学科评估和治疗规划提供参考。甲基化循环肿瘤DNA阴性可能提示肝脏干预的最佳时机，而阳性可能提示化疗的启动或重新调整，或立即进行局部干预。我们的结果证实术后甲基化循环肿瘤DNA阴性是生存的强预后标志物。
