Plasma microRNA are disease response biomarkers in classical Hodgkin lymphoma

Jones, Kimberley, Nourse, Jamie P., Keane, Colm, Bhatnagar, Atul and Gandhi, Maher K. (2014) Plasma microRNA are disease response biomarkers in classical Hodgkin lymphoma. Clinical Cancer Research, 20 1: 253-264. doi:10.1158/1078-0432.CCR-13-1024


Author Jones, Kimberley
Nourse, Jamie P.
Keane, Colm
Bhatnagar, Atul
Gandhi, Maher K.
Title Plasma microRNA are disease response biomarkers in classical Hodgkin lymphoma
Journal name Clinical Cancer Research   Check publisher's open access policy
ISSN 1078-0432
1557-3265
Publication date 2014-01-01
Year available 2013
Sub-type Article (original research)
DOI 10.1158/1078-0432.CCR-13-1024
Volume 20
Issue 1
Start page 253
End page 264
Total pages 12
Place of publication Philadelphia, PA, United States
Publisher American Association for Cancer Research
Collection year 2014
Language eng
Formatted abstract
Purpose: Although microRNAs (miRNA) show potential as diagnostic biomarkers in cancer, their role as circulating cell-free disease response biomarkers remains unknown. Candidate circulating miRNA biomarkers for classical Hodgkin lymphoma (cHL) might arise from Hodgkin–Reed–Sternberg (HRS) cells and/or nonmalignant tumor-infiltrating cells. HRS cells are sparse within the diseased node, embedded within a benign microenvironment, the composition of which is distinct from that seen in healthy lymph nodes.
Experimental Design: Microarray profiling of more than 1,000 human miRNAs in 14 cHL primary tissues and eight healthy lymph nodes revealed a number of new disease node–associated miRNAs, including miR-494 and miR-1973. Using quantitative real-time PCR (qRT-PCR), we tested the utility of these, as well as previously identified disease node–associated plasma miRNAs (including miR-21 and miR-155), as disease response biomarkers in a prospective cohort of 42 patients with cHL. Blood samples were taken in conjunction with radiologic imaging at fixed time points before, during, and after therapy. Absolute quantification was used so as to facilitate implementation in diagnostic laboratories.
Results: Levels of miR-494, miR-1973, and miR-21 were higher in patients than control (n = 20) plasma (P = 0.004, P = 0.007, and P < 0.0001, respectively). MiR-494 and miR-21 associated with Hasenclever scores ≥3. Strikingly, all three miRNAs returned to normal at remission (P = 0.0006, P = 0.0002, and P < 0.0001 respectively). However, only miR-494 and miR-1973 reflected interim therapy response with reduction being more pronounced in patients achieving complete versus partial responses (P = 0.043 and P = 0.0012, respectively).
Conclusion: Our results demonstrate that in patients with cHL, circulating cell-free miRNAs can reflect disease response once therapy has commenced.
Keyword B-cell lymphoma
International prognostic score
Barr virus DNA
Circulating micrornas
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online 12 November 2013

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
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