Serum MicroRNAs in HIV-infected individuals as pre-diagnosis biomarkers for AIDS-NHL

Dharma R. Thapa, Shehnaz K. Hussain, Wen Ching Tran, Gypsyamber D'souza, Jay H. Bream, Chad J. Achenback, Velpandi Ayyavoo, Roger Detels, Otoniel Martínez-Maza

Research output: Contribution to journalArticle

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). Design: 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.

Original languageEnglish (US)
Pages (from-to)229-237
Number of pages9
JournalJournal of acquired immune deficiency syndromes
Volume66
Issue number2
DOIs
StatePublished - Jun 1 2014

Keywords

  • HIV
  • lymphoma
  • miR-122
  • miR-21
  • miR-222
  • miR-223

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

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    Thapa, D. R., Hussain, S. K., Tran, W. C., D'souza, G., Bream, J. H., Achenback, C. J., Ayyavoo, V., Detels, R., & Martínez-Maza, O. (2014). Serum MicroRNAs in HIV-infected individuals as pre-diagnosis biomarkers for AIDS-NHL. Journal of acquired immune deficiency syndromes, 66(2), 229-237. https://doi.org/10.1097/QAI.0000000000000146