1. Consistent high concentration of the viral microRNA BART17 in plasma samples from nasopharyngeal carcinoma patients - evidence of non-exosomal transport
- Author
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Ana Barat, Arij Ben Chaaben, François-Régis Ferrand, Aurore Gelin, Charles-Henry Gattolliat, Claire Gourzones, Fethi Guemira, Corinne Amiel, Joël Guigay, Anne-Sophie Jimenez-Pailhes, Philippe Lang, Jihène Klibi, Maryse Guerin, Véronique Schneider, Benjamin Verillaud, Philippe Busson, Interactions moléculaires et cancer ( IMC (UMR 8126) ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Centre National de la Recherche Scientifique ( CNRS ), École du Val de Grâce ( EVDG ), Service de Santé des Armées, Service de virologie, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], Service ORL, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Lariboisière, Dyslipidémies, inflammation et athérosclérose dans les maladies métaboliques, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Clinical Biology Department, Institut Salah Azaiz, Département de cancérologie cervico-faciale [Gustave Roussy] ( CCF ), Institut Gustave Roussy ( IGR ), Service de Radiothérapie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], This study was supported by grants from the Gustave Roussy Foundation (Head and Neck tumors - 2011), the Institut National du Cancer (INCa-DHOS translational grant) and the Ligue Nationale contre le Cancer (comité du Val de Marne). CG was supported by the Association pour la Recherche sur le Cancer., BMC, Ed., Interactions moléculaires et cancer (IMC (UMR 8126)), Signalisation, noyaux et innovations en cancérologie (UMR8126), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), École du Val de Grâce (EVDG), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de cancérologie cervico-faciale [Gustave Roussy] (CCF), Institut Gustave Roussy (IGR), Service d'Oncologie Radiothérapie [CHU Pitié Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
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Male ,Herpesvirus 4, Human ,medicine.disease_cause ,Exosomes ,Plasma ,0302 clinical medicine ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,0303 health sciences ,microRNA ,Middle Aged ,3. Good health ,[ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Real-time polymerase chain reaction ,Infectious Diseases ,030220 oncology & carcinogenesis ,[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,RNA, Viral ,Female ,Adult ,Lipoproteins ,Nasopharyngeal neoplasm ,miR-BART ,Biology ,Real-Time Polymerase Chain Reaction ,Exosome ,03 medical and health sciences ,Virology ,Head and Neck carcinomas ,medicine ,Carcinoma ,Nasopharyngeal carcinoma ,Humans ,Epstein-Barr virus ,030304 developmental biology ,Aged ,Research ,Biological Transport ,Nasopharyngeal Neoplasms ,Biomarker ,medicine.disease ,Epstein–Barr virus ,Head and neck squamous-cell carcinoma ,Microvesicles ,MicroRNAs ,DNA, Viral ,Biomarkers ,DNA load - Abstract
Background Because latent Epstein Barr (EBV)-infection is a specific characteristic of malignant nasopharyngeal carcinoma (NPC), various molecules of viral origin are obvious candidate biomarkers in this disease. In a previous study, we could show in a few clinical samples that it was possible to detect a category of EBV microRNAs called miR-BARTs in the plasma of at least a fraction of NPC patients. The first aim of the present study was to investigate the status of circulating miR-BART17-5p (one of the miR-BARTs hereafter called miR-BART17) and EBV DNA in a larger series of NPC plasma samples. The second aim was to determine whether or not circulating miR-BART17 was carried by plasma exosomes. Patients and methods Plasma samples were collected from 26 NPC patients and 10 control donors, including 9 patients with non-NPC Head and Neck squamous cell carcinoma and one healthy EBV carrier. Concentrations of miR-BART17 and two cellular microRNAs (hsa-miR-16 and -146a) were assessed by real-time quantitative PCR with spike-in normalization and absolute quantification. In addition, for 2 patients, exosome distributions of miR-BART17 and miR-16 were investigated following plasma lipoprotein fractionation by isopycnic density gradient ultrcentrifugation. Results The miR-BART17 was significantly more abundant in plasma samples from NPC patients compared to non-NPC donors. Above a threshold of 506 copies/mL, detection of miR-BART17 was highly specific for NPC patients (ROC curve analysis: AUC=0.87 with true positive rate = 0.77, false positive rate = 0.10). In this relatively small series, the concentration of plasma miR-BART17 and the plasma EBV DNA load were not correlated. When plasma samples were fractionated, miR-BART17 co-purified with a protein-rich fraction but not with exosomes. Conclusions Detection of high concentrations of plasma miR-BART17 is consistent in NPC patients. This parameter is, at least in part, independent of the viral DNA load. Circulating miR-BART17 does not co-purify with exosomes.
- Published
- 2013