1. Risk, Diagnostic and Predictor Factors for Classical Hodgkin Lymphoma in HIV-1-Infected Individuals: Role of Plasma Exosome-Derived miR-20a and miR-21
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Francisco Tejerina-Picado, Ana Moreno, José L. Casado, María José Galindo, Asunción Hernando, Fernando Dronda, María J Pérez-Elías, Víctor Asensi, Manuel Leal, Yolanda M. Pacheco, José Hermida, Alejandro Vallejo, Esther Vázquez, Francisco J Hernández-Walias, José M Rodríguez-Fernández, Carmen Quereda, Santiago Moreno, [Hernández-Walias,FJ, Vázquez,E, Pérez-Elías,MJ, Dronda,F, Casado,JL, Moreno,A, Hermida,JM, Quereda,C, Moreno,S, Vallejo,A] Laboratory of Immunovirology, Infectious Diseases Department, Health Research Institute Ramon y Cajal (IRyCIS), Ramon y Cajal University Hospital, Madrid, Spain. [Pacheco,Y, Leal,M] Biomedicine Institute of Seville (IBiS), University Hospital Virgen del Rocío, Seville, Spain. [Rodríguez-Fernández,JM] Department of Internal Medicine, Gómez Ulla Central Hospital, Madrid, Spain. [Hernando,A] Department of Medicine, 12 de Octubre University Hospital, Universidad European University of Madrid, Instituto de Investigación Hospital 12 de Octubre (imas12), Madrid, Spain. [Tejerina-Picado,F] Gregorio Marañón University General Hospital, Madrid, Spain. [Asensi,V] Infectious Diseases Department, Central University Hospital of Asturias, University Medical School, Oviedo, Spain. [Asensi,V] Group of Translational Research in Infectious Diseases, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain. [Galindo,MJ] Clinic University Hospital of Valencia, Valencia, Spain. [Leal,M] Department of Internal Medicine and Infectious Diseases, Viamed Hospital, Santa Ángela de la Cruz, Seville, Spain., and Instituto de Salud Carlos III, Spanish Health Ministry, with Grant numbers PI10-1077 and PI15-657. The HIV BioBank, integrated in the Spanish AIDS Research Network, is supported by Instituto de Salud Carlos III, Spanish Healt Ministry (Grant nº D06/0006/0035, RD12/0017/0037 and RD16/0025/0019) as part of the Plan Nacional R+D+I and cofinanced by ISCIII- Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER). This study (RIS-EPICLIN-03/2010) would not have been possible without the collaboration of all the patients, medical and nursery staff and data managers who have taken part in the project. The RIS Cohort (CoRIS) is funded by the Instituto de Salud Carlos III through the Red Temática de Investigación Cooperativa en SIDA (RIS C03/173, RD12/0017/0018 and RD16/0002/0006) as part of the Plan Nacional R+D+I and cofinanced by ISCIII-Subdirección General de Evaluacion y el Fondo Europeo de Desarrollo Regional (FEDER).
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Exosome miRs ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies::Retrospective Studies [Medical Subject Headings] ,medicine.medical_treatment ,lcsh:Medicine ,Likelihood ratios in diagnostic testing ,Gastroenterology ,Exosomas ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,Tratamiento médico ,0302 clinical medicine ,immune system diseases ,Information Science::Information Science::Data Collection::Vital Statistics::Morbidity::Incidence [Medical Subject Headings] ,hemic and lymphatic diseases ,Anatomy::Cells::Antibody-Producing Cells::B-Lymphocytes [Medical Subject Headings] ,cell phenotyping ,polycyclic compounds ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Intercellular Signaling Peptides and Proteins::Cytokines::Interleukins::Interleukin-6 [Medical Subject Headings] ,Tecnología médica ,MicroARNs ,0303 health sciences ,education.field_of_study ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings] ,Incidence (epidemiology) ,Diseases::Neoplasms::Neoplasms by Histologic Type::Lymphoma::Hodgkin Disease [Medical Subject Headings] ,food and beverages ,General Medicine ,Cáncer ,030220 oncology & carcinogenesis ,Enfermedad de Hodgkin ,Biomarker (medicine) ,Anatomy::Hemic and Immune Systems::Blood::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::Killer Cells, Natural [Medical Subject Headings] ,Anatomy::Cells::Cellular Structures::Intracellular Space::Cytoplasm::Cytoplasmic Structures::Organelles::Cytoplasmic Vesicles::Transport Vesicles::Exosomes [Medical Subject Headings] ,exosome miRs ,medicine.medical_specialty ,Sida ,Population ,macromolecular substances ,Exosome ,Article ,03 medical and health sciences ,Internal medicine ,VIH (Virus) ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Immunologic Techniques::Immunologic Tests::Immunophenotyping [Medical Subject Headings] ,medicine ,Classical Hodgkin lymphoma ,Persons::Persons::Age Groups::Adult [Medical Subject Headings] ,education ,030304 developmental biology ,Geographical Locations::Geographic Locations::Europe::Spain [Medical Subject Headings] ,Chemotherapy ,Organisms::Viruses::RNA Viruses::Retroviridae::Lentivirus::Lentiviruses, Primate::HIV::HIV-1 [Medical Subject Headings] ,business.industry ,lcsh:R ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Area Under Curve [Medical Subject Headings] ,Cancer ,biomarkers ,Andalucía ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Immunologic::Receptors, Cytokine::Receptors, Tumor Necrosis Factor::Receptors, Tumor Necrosis Factor, Type I [Medical Subject Headings] ,medicine.disease ,Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Antisense Elements (Genetics)::RNA, Antisense::MicroRNAs [Medical Subject Headings] ,Biomarcadores ,Inmunofenotipificación ,HIV-1 ,Cell phenotyping ,business ,Biomarkers ,Hodgkin lymphoma - Abstract
The incidence of classical Hodgkin lymphoma (cHL) in the HIV-1 setting has increased 5&ndash, 25-fold compared to that observed in the general population. This study aimed to determine whether selected micro RNAs (miRs) and other soluble biomarkers and cellular subsets are dysregulated in cHL and could be used as biomarkers. This was a retrospective and longitudinal matched case-control study of 111 Caucasian, HIV-1-infected adult individuals, including 37 individuals with cHL and 74 with no type of cancer. Immunovirological data, plasma exosome-derived miR-16, miR-20a, miR-21, miR-221, miR-223, miR-106a, miR-185, miR-23, miR-30d, miR-222, miR-146a and miR-324, plasma IL-6, sCD14, sCD27, sCD30, sIL-2R, TNFR1, and cell phenotyping of T and B lymphocytes and natural killer (NK) cells were analyzed. Before cHL diagnosis, miR-20a, miR-21, and sCD30 were higher in cHL (p = 0.008, p = 0.009 and p = 0.042, respectively), while miR-16 was down-regulated (p = 0.040). miR-20a and miR-21 were independently associated with cHL (p = 0.049 and p = 0.035, respectively). The combination of miR-20a and miR-21 showed a good AUC value of 0.832 with a moderate likelihood ratio positive (LR+) value of 5.6 and a slight likelihood ratio negative (LR&minus, ) value of 0.23. At cHL diagnosis, miR-20a, miR-21 and miR-324 were overexpressed in cHL (p = 0.005, p = 0.024, and p = 0.001, respectively), while miR-223, miR-16, miR-185 and miR-106a were down regulated (p = 0.042, p = 0.007, p = 0.006, and p = 0.002, respectively). In addition, sCD14, sCD27, sCD30 and IL2R levels were higher in these individuals (p = 0.038, p = 0.010, p = 0.030, p = 0.006, respectively). miR-20a was independently associated with cHL (p = 0.011). The diagnostic value of miR-20a showed good AUC value of 0.754 (p = 0.074) with a slight LR+ value of 2 and a slight LR&minus, of 0.25. After chemotherapy, miR-20a was higher in those individuals who had an adverse outcome (p <, 0.001), while sCD14 and sCD30 were higher (p <, 0.001). A specific signature of miRs and cytokines associated with a subsequent cHL diagnosis was found in this study, especially miR-20a and miR-21. Also, another biomarker signature was found at cHL diagnosis, with a relevant discriminant disease value for miR-20a. Of note, miR-20a expression was higher in those individuals who had an adverse clinical outcome after chemotherapy.
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- 2020