Autor: |
Hernández-Walias FJ; Laboratory of Immunovirology, Infectious Diseases Department. Health Research Institute Ramon y Cajal (IRyCIS), Ramon y Cajal University Hospital, 28034 Madrid, Spain., Vázquez E; Laboratory of Immunovirology, Infectious Diseases Department. Health Research Institute Ramon y Cajal (IRyCIS), Ramon y Cajal University Hospital, 28034 Madrid, Spain., Pacheco Y; Biomedicine Institute of Seville (IBiS), University Hospital Virgen del Rocío, 41013 Seville, Spain., Rodríguez-Fernández JM; Department of Internal Medicine. Gómez Ulla Central Hospital, 28047 Madrid, Spain., Pérez-Elías MJ; Laboratory of Immunovirology, Infectious Diseases Department. Health Research Institute Ramon y Cajal (IRyCIS), Ramon y Cajal University Hospital, 28034 Madrid, Spain., Dronda F; Laboratory of Immunovirology, Infectious Diseases Department. Health Research Institute Ramon y Cajal (IRyCIS), Ramon y Cajal University Hospital, 28034 Madrid, Spain., Casado JL; Laboratory of Immunovirology, Infectious Diseases Department. Health Research Institute Ramon y Cajal (IRyCIS), Ramon y Cajal University Hospital, 28034 Madrid, Spain., Moreno A; Laboratory of Immunovirology, Infectious Diseases Department. Health Research Institute Ramon y Cajal (IRyCIS), Ramon y Cajal University Hospital, 28034 Madrid, Spain., Hermida JM; Laboratory of Immunovirology, Infectious Diseases Department. Health Research Institute Ramon y Cajal (IRyCIS), Ramon y Cajal University Hospital, 28034 Madrid, Spain., Quereda C; Laboratory of Immunovirology, Infectious Diseases Department. Health Research Institute Ramon y Cajal (IRyCIS), Ramon y Cajal University Hospital, 28034 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), 28041 Madrid, Spain., Tejerina-Picado F; Gregorio Marañón University General Hospital, 28007 Madrid, Spain., Asensi V; Infectious Diseases Department, Central University Hospital of Asturias, University Medical School, 33011 Oviedo, Spain.; Group of Translational Research in Infectious Diseases, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain., Galindo MJ; Clinic University Hospital of Valencia, 46010 Valencia, Spain., Leal M; Biomedicine Institute of Seville (IBiS), University Hospital Virgen del Rocío, 41013 Seville, Spain.; Department of Internal Medicine and Infectious Diseases, Viamed Hospital, Santa Ángela de la Cruz, 41014 Seville, Spain., Moreno S; Laboratory of Immunovirology, Infectious Diseases Department. Health Research Institute Ramon y Cajal (IRyCIS), Ramon y Cajal University Hospital, 28034 Madrid, Spain., Vallejo A; Laboratory of Immunovirology, Infectious Diseases Department. Health Research Institute Ramon y Cajal (IRyCIS), Ramon y Cajal University Hospital, 28034 Madrid, Spain. |
Abstrakt: |
The incidence of classical Hodgkin lymphoma (cHL) in the HIV-1 setting has increased 5-25-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-) 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- 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. |