Beschreibung:
<jats:title>Abstract</jats:title><jats:sec>
<jats:title>Background</jats:title>
<jats:p>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).</jats:p>
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<jats:title>Methods</jats:title>
<jats:p>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 <jats:italic>NPTX2</jats:italic>, <jats:italic>SPARC</jats:italic>, <jats:italic>BMP3</jats:italic>, <jats:italic>SFRP1</jats:italic> and <jats:italic>TFPI2</jats:italic> genes were measured using digital droplet PCR (ddPCR). BEAMing technique was performed for quantitation of <jats:italic>RAS</jats:italic> mutations in cfDNA, and CA19-9 was measured using standard techniques.</jats:p>
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<jats:title>Results</jats:title>
<jats:p><jats:italic>NPTX2</jats:italic> was the most highly and frequently methylated gene in cfDNA samples from mPDAC patients. Higher circulating <jats:italic>NPTX2</jats:italic> methylation levels at diagnosis were associated with poor prognosis and efficiently stratified patients for prediction of overall survival (6.06% cut-off, <jats:italic>p</jats:italic> = 0.0067). Dynamics of circulating <jats:italic>NPTX2</jats:italic> 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 <jats:italic>NPTX2</jats:italic> methylation levels.</jats:p>
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<jats:title>Conclusions</jats:title>
<jats:p>Our study supports circulating <jats:italic>NPTX2</jats:italic> methylation levels as a promising liquid biopsy-based clinical tool for non-invasive prognosis, monitoring disease evolution and response to treatment in mPDAC patients.</jats:p>
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