Hussung Saskia, Hess Maria E, Haghighi Elham Bavafaye, Wittel Uwe A, Boerries Melanie, Fritsch Ralph M
Department of Medicine I (Hematology, Oncology and Stem Cell Transplantation), Freiburg University Medical Center, 79106 Freiburg, Germany.
Department of Medical Oncology and Hematology, Zurich University Hospital, 8091 Zurich, Switzerland.
Diagnostics (Basel). 2024 Dec 28;15(1):49. doi: 10.3390/diagnostics15010049.
Given the poor prognosis of metastatic pancreatic adenocarcinoma (mPDAC), closer disease monitoring through liquid biopsy, most frequently based on serial measurements of cell-free mutated ( cfDNA), has become a highly active research focus, aimed at improving patients' long-term outcomes. However, most of the available data show only a limited predictive and prognostic value of single-parameter-based methods. We hypothesized that a combined longitudinal analysis of cfDNA and novel protein biomarkers could improve risk stratification and molecular monitoring of patients with mPDAC. We prospectively collected 160 plasma samples from 47 patients with mPDAC at our institution. Highly sensitive single-target ddPCR assays were employed to detect and quantify cfDNA. Additionally, analysis of ten protein biomarkers was performed through Enzyme-linked Immunosorbent Assay (ELISA), and Carbohydrate-Antigen 19-9 (CA 19-9) dynamics were registered. : cfDNA was detectable in 37/47 (78.7%) patients throughout the course of study, and CA 19-9 levels were elevated in 40 out of 47 (85.1%) patients. cfDNA increase at the time of the first follow-up could predict inferior progression-free survival (PFS) (Hazard ratio (HR) = 3.40, = 0.0003) and overall survival (OS) (HR = 4.91, < 0.0001). In contrast to CA 19-9 kinetics, which were not predictive of outcome, integrated analysis of cfDNA combined with six evaluated circulating protein biomarkers allowed basal risk stratification at the time of the first follow-up (HR = 10.2, = 0.0014). : A combined longitudinal analysis of cfDNA with selected protein biomarkers offers significantly improved prognostic value for patients with mPDAC compared to single-parameter methods. This innovative approach is a step forward in the molecular monitoring of mPDAC and should be validated in further prospective studies.
鉴于转移性胰腺腺癌（mPDAC）预后较差，通过液体活检进行更密切的疾病监测（最常见的是基于对游离突变（cfDNA）的系列测量）已成为一个高度活跃的研究重点，旨在改善患者的长期预后。然而，大多数现有数据显示基于单参数的方法仅具有有限的预测和预后价值。我们假设对cfDNA和新型蛋白质生物标志物进行联合纵向分析可以改善mPDAC患者的风险分层和分子监测。我们在本机构前瞻性地收集了47例mPDAC患者的160份血浆样本。采用高灵敏度单靶点数字PCR检测法来检测和定量cfDNA。此外，通过酶联免疫吸附测定（ELISA）对十种蛋白质生物标志物进行分析，并记录糖类抗原19-9（CA 19-9）的动态变化。在整个研究过程中，37/47（78.7%）的患者可检测到cfDNA，47例患者中有40例（85.1%）的CA 19-9水平升高。首次随访时cfDNA增加可预测无进展生存期（PFS）较差（风险比（HR）=3.40，P=0.0003）和总生存期（OS）较差（HR=4.91，P<0.0001）。与不具有预后预测价值的CA 19-9动力学不同，cfDNA与六种评估的循环蛋白质生物标志物的综合分析可在首次随访时进行基础风险分层（HR=10.2，P=0.0014）。与单参数方法相比，对cfDNA与选定的蛋白质生物标志物进行联合纵向分析可为mPDAC患者提供显著改善的预后价值。这种创新方法是mPDAC分子监测方面的一大进步，应在进一步的前瞻性研究中进行验证。
