title: Serum microRNAs in HIV-infected individuals as pre-diagnosis biomarkers for AIDS-NHL.
abstract: OBJECTIVE
  To determine if changes in levels of serum microRNAs (miRNAs) were seen preceding the diagnosis of AIDS-related non-Hodgkin lymphoma (AIDS-NHL).
  
  
  METHODS
  Serum miRNA levels were compared in 3 subject groups from the Multicenter AIDS Cohort Study: HIV-negative men (n = 43), HIV-positive men who did not develop NHL (n = 45), and HIV-positive men before AIDS-NHL diagnosis (n = 62, median time before diagnosis, 8.8 months).
  
  
  METHODS
  A total of 175 serum-enriched miRNAs were initially screened to identify differentially expressed miRNAs among these groups and the results validated by quantitative polymerase chain reaction. Receiver-operating characteristic analysis was then performed to assess biomarker utility.
  
  
  RESULTS
  Higher levels of miR-21 and miR-122, and a lower level of miR-223, were able to discriminate HIV-infected from the HIV-uninfected groups, suggesting that these miRNAs are biomarkers for HIV infection but are not AIDS-NHL specific. Among the HIV-infected groups, a higher level of miR-222 was able to discriminate diffuse large B-cell lymphoma (DLBCL) and primary central nervous system lymphoma (PCNSL) subjects from HIV-infected subjects who did not develop NHL, with area under the receiver-operating characteristic curve of 0.777 and 0.792, respectively. At miR-222 cutoff values of 0.105 for DLBCL and 0.109 for PCNSL, the sensitivity and specificity were 75% and 77%, and 80% and 82%, respectively.
  
  
  CONCLUSIONS
  Altered serum levels of miR-21, miR-122, and miR-223 are seen in HIV-infected individuals. Higher serum level of miR-222 has clear potential as a serum biomarker for earlier detection of DLBCL and PCNSL among HIV-infected individuals.
authors.affiliation: *University of California, Los Angeles, AIDS Institute, Los Angeles, CA; Departments of †Obstetrics and Gynecology; ‡Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA; §Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA; ‖Department of Epidemiology, University of California, Los Angeles, Fielding School of Public Health, Los Angeles, CA; Departments of ¶Epidemiology; #Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; **Division of Infectious Diseases, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL; and ††Department of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA.
authors.forename: Dharma R
authors.initials: DR
authors.lastname: Thapa
authors.forename: Shehnaz K
authors.initials: SK
authors.lastname: Hussain
authors.forename: Wen-Ching
authors.initials: WC
authors.lastname: Tran
authors.forename: Gypsyamber
authors.initials: G
authors.lastname: Dʼsouza
authors.forename: Jay H
authors.initials: JH
authors.lastname: Bream
authors.forename: Chad J
authors.initials: CJ
authors.lastname: Achenback
authors.forename: Velpandi
authors.initials: V
authors.lastname: Ayyavoo
authors.forename: Roger
authors.initials: R
authors.lastname: Detels
authors.forename: Otoniel
authors.initials: O
authors.lastname: Martínez-Maza
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D018791:CD4 Lymphocyte Count; D015658:HIV Infections / Q000097:blood / Q000175:diagnosis*; D006801:Humans; D016483:Lymphoma, AIDS-Related / Q000097:blood / Q000175:diagnosis*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000097:blood / Q000175:diagnosis; D008228:Lymphoma, Non-Hodgkin / Q000097:blood / Q000175:diagnosis; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D011446:Prospective Studies; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs