外周和门静脉KRAS ctDNA检测作为胰管腺癌早期肿瘤复发的独立预后标志物。
Peripheral and Portal Venous KRAS ctDNA Detection as Independent Prognostic Markers of Early Tumor Recurrence in Pancreatic Ductal Adenocarcinoma.
发表日期：2023 Mar 01
作者：
Christine Nitschke, Benedikt Markmann, Philipp Walter, Anita Badbaran, Marie Tölle, Jolanthe Kropidlowski, Yassine Belloum, Mara R Goetz, Jan Bardenhagen, Louisa Stern, Joseph Tintelnot, Martin Schönlein, Marianne Sinn, Paul van der Leest, Ronald Simon, Asmus Heumann, Jakob R Izbicki, Klaus Pantel, Harriet Wikman, Faik G Uzunoglu
来源：
CLINICAL CHEMISTRY
摘要：
KRAS循环肿瘤DNA（ctDNA）已经显示出在胰腺导管腺癌（PDAC）中的生物标志物潜力，但尚未在临床常规中应用。我们旨在提高ctDNA检测在PDAC中的临床适用性，并研究抽血部位和时间点对KRAS突变的检测和预后作用的影响。其中包括108名PDAC患者（65例治愈，43例姑息）的221个血样。分析基线外周和肿瘤引流门静脉（PV），手术后和随访血液，并与预后相关联。我们发现，姑息患者基线血液中KRAS突变检测率和拷贝数显著高于治愈患者（58.1% vs 24.6%; P = 0.002; and P < 0.001）。与基线相比，PV中发现了显著更高的KRAS突变拷贝数（P < 0.05）。术前、术后和PV中发现的KRAS检测与较短的无复发生存期显著相关（所有P < 0.015）并被确认为独立的预后标志物。在治愈和姑息队列中，KRAS ctDNA状态也是较短的总生存率的独立不利预后因子（危险比[HR]分别为4.9，P = 0.011; HR 6.9，P = 0.008）。KRAS ctDNA的检测是治愈和姑息PDAC患者的独立不良预后标志物，适用于所有血液采集部位，并且是强有力的随访标志物。其中最重要的预后影响在PV血样中观察到，这可能是识别边缘预后患者的有效新工具，引导将来关于新辅助治疗的决策。此外，更高的PV突变拷贝数有助于提高技术可行性。©American Association for Clinical Chemistry 2023.
KRAS circulating tumor DNA (ctDNA) has shown biomarker potential for pancreatic ductal adenocarcinoma (PDAC) but has not been applied in clinical routine yet. We aim to improve clinical applicability of ctDNA detection in PDAC and to study the impact of blood-draw site and time point on the detectability and prognostic role of KRAS mutations.221 blood samples from 108 PDAC patients (65 curative, 43 palliative) were analyzed. Baseline peripheral and tumor-draining portal venous (PV), postoperative, and follow-up blood were analyzed and correlated with prognosis.Significantly higher KRAS mutant detection rates and copy numbers were observed in palliative compared to curative patients baseline blood (58.1% vs 24.6%; P = 0.002; and P < 0.001). Significantly higher KRAS mutant copies were found in PV blood compared to baseline (P < 0.05) samples. KRAS detection in pre- and postoperative and PV blood were significantly associated with shorter recurrence-free survival (all P < 0.015) and identified as independent prognostic markers. KRAS ctDNA status was also an independent unfavorable prognostic factor for shorter overall survival in both palliative and curative cohorts (hazard ratio [HR] 4.9, P = 0.011; HR 6.9, P = 0.008).KRAS ctDNA detection is an independent adverse prognostic marker in curative and palliative PDAC patients-at all sites of blood draw and a strong follow-up marker. The most substantial prognostic impact was seen for PV blood, which could be an effective novel tool for identifying prognostic borderline patients-guiding future decision-making on neoadjuvant treatment despite anatomical resectability. In addition, higher PV mutant copy numbers contribute to an improved technical feasibility.©American Association for Clinical Chemistry 2023.