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

Clinical Epigenetics

Research

Pablo Cano-Ramírez¹  María Victoria García-Ortiz²  Marta Toledano-Fonseca²  Silvia Guil-Luna³  Antonio Rodríguez-Ariza⁴  María Auxiliadora Gómez-España⁴  Enrique Aranda⁵  María Teresa Cano⁶  Elizabeth Inga-Saavedra⁶  Rosa María Rodríguez-Alonso⁷ 

[1] Maimónides Biomedical Research Institute of Córdoba (IMIBIC), Córdoba, Spain;Andalusia-Roche Network Mixed Alliance in Precision Medical Oncology, Seville, Spain;Maimónides Biomedical Research Institute of Córdoba (IMIBIC), Córdoba, Spain;Andalusia-Roche Network Mixed Alliance in Precision Medical Oncology, Seville, Spain;Cancer Network Biomedical Research Center (CIBERONC), Madrid, Spain;Maimónides Biomedical Research Institute of Córdoba (IMIBIC), Córdoba, Spain;Andalusia-Roche Network Mixed Alliance in Precision Medical Oncology, Seville, Spain;Cancer Network Biomedical Research Center (CIBERONC), Madrid, Spain;Department of Anatomy and Comparative Pathology, University of Córdoba, Córdoba, Spain;Maimónides Biomedical Research Institute of Córdoba (IMIBIC), Córdoba, Spain;Andalusia-Roche Network Mixed Alliance in Precision Medical Oncology, Seville, Spain;Cancer Network Biomedical Research Center (CIBERONC), Madrid, Spain;Medical Oncology Department, Reina Sofía University Hospital, Córdoba, Spain;Maimónides Biomedical Research Institute of Córdoba (IMIBIC), Córdoba, Spain;Andalusia-Roche Network Mixed Alliance in Precision Medical Oncology, Seville, Spain;Cancer Network Biomedical Research Center (CIBERONC), Madrid, Spain;Medical Oncology Department, Reina Sofía University Hospital, Córdoba, Spain;Department of Medicine, Faculty of Medicine, University of Córdoba, Córdoba, Spain;Maimónides Biomedical Research Institute of Córdoba (IMIBIC), Córdoba, Spain;Andalusia-Roche Network Mixed Alliance in Precision Medical Oncology, Seville, Spain;Medical Oncology Department, Reina Sofía University Hospital, Córdoba, Spain;Medical Oncology Department, Reina Sofía University Hospital, Córdoba, Spain;

关键词: NPTX2;    Pancreatic ductal adenocarcinoma;    Prognostic biomarker;    Epigenetic biomarker;    Liquid biopsy;    DNA methylation;    ddPCR;    RAS;    CA19-9;   

DOI  :  10.1186/s13148-023-01535-4

 received in 2023-04-12, accepted in 2023-07-16,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundPancreatic 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).MethodsPlasma 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.ResultsNPTX2 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.ConclusionsOur 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.

【 授权许可】

CC BY   
© The Author(s) 2023

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