循环NPTX2甲基化作为转移性胰腺癌症预后和监测的非侵入性生物标志物。

IF 5.7 2区 医学 Q1 Medicine Clinical Epigenetics Pub Date : 2023-07-22 DOI:10.1186/s13148-023-01535-4
María Victoria García-Ortiz, Pablo Cano-Ramírez, Marta Toledano-Fonseca, María Teresa Cano, Elizabeth Inga-Saavedra, Rosa María Rodríguez-Alonso, Silvia Guil-Luna, María Auxiliadora Gómez-España, Antonio Rodríguez-Ariza, Enrique Aranda
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引用次数: 1

摘要

背景:癌症是最致命的癌症,预后极差,主要是诊断晚期和治疗无效。CA19-9水平和计算机断层扫描(CT)成像是评估疾病进展和治疗反应的主要标准。在这项研究中,我们探索了基于液体活检的表观遗传学生物标志物,用于转移性胰腺导管腺癌(mPDAC)患者的预后和疾病监测。方法:在诊断时收集44名mPDAC患者的血浆样本,其中15人在疾病随访期间获得了额外的样本。在无细胞DNA(cfDNA)后,使用数字液滴PCR(ddPCR)测量甲基化NPTX2、SPARC、BMP3、SFRP1和TFPI2基因的分离循环水平。BEAMing技术用于定量cfDNA中的RAS突变,CA19-9使用标准技术进行测量。结果:在mPDAC患者的cfDNA样本中,NPTX2是甲基化程度最高、频率最高的基因。诊断时较高的循环NPTX2甲基化水平与预后不良相关,并有效地对患者进行分层预测总生存率(6.06%的临界值,p = 0.0067)。循环NPTX2甲基化水平的动力学与疾病进展和对治疗的反应相关,并且比CA19-9更好地预测mPDAC患者的疾病演变。值得注意的是,在许多情况下,CT扫描检测到的疾病进展是通过循环NPTX2甲基化水平的增加来预测的。结论:我们的研究支持循环NPTX2甲基化水平作为一种有前途的基于液体活检的临床工具,用于mPDAC患者的无创预后、监测疾病演变和治疗反应。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Circulating NPTX2 methylation as a non-invasive biomarker for prognosis and monitoring of metastatic pancreatic cancer.

Background: Pancreatic cancer is the most lethal cancer with a dismal prognosis mainly due to diagnosis at advanced stage and ineffective treatments. CA19-9 levels and computed tomography (CT) imaging are the main standard criteria for evaluating disease progression and treatment response. In this study we explored liquid biopsy-based epigenetic biomarkers for prognosis and monitoring disease in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC).

Methods: Plasma samples were collected from 44 mPDAC patients at the time of diagnosis, and in 15 of them, additional samples were obtained during follow-up of the disease. After cell-free DNA (cfDNA), isolation circulating levels of methylated NPTX2, SPARC, BMP3, SFRP1 and TFPI2 genes were measured using digital droplet PCR (ddPCR). BEAMing technique was performed for quantitation of RAS mutations in cfDNA, and CA19-9 was measured using standard techniques.

Results: NPTX2 was the most highly and frequently methylated gene in cfDNA samples from mPDAC patients. Higher circulating NPTX2 methylation levels at diagnosis were associated with poor prognosis and efficiently stratified patients for prediction of overall survival (6.06% cut-off, p = 0.0067). Dynamics of circulating NPTX2 methylation levels correlated with disease progression and response to therapy and predicted better than CA19-9 the evolution of disease in mPDAC patients. Remarkably, in many cases the disease progression detected by CT scan was anticipated by an increase in circulating NPTX2 methylation levels.

Conclusions: Our study supports circulating NPTX2 methylation levels as a promising liquid biopsy-based clinical tool for non-invasive prognosis, monitoring disease evolution and response to treatment in mPDAC patients.

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来源期刊
Clinical Epigenetics
Clinical Epigenetics Biochemistry, Genetics and Molecular Biology-Developmental Biology
CiteScore
8.90
自引率
5.30%
发文量
150
审稿时长
12 weeks
期刊介绍: Clinical Epigenetics, the official journal of the Clinical Epigenetics Society, is an open access, peer-reviewed journal that encompasses all aspects of epigenetic principles and mechanisms in relation to human disease, diagnosis and therapy. Clinical trials and research in disease model organisms are particularly welcome.
期刊最新文献
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