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Pre-transplant expressions of microRNAs, comorbidities, and post-transplant mortality

Bone Marrow Transplantation volume 54, pages 973–979 (2019)Cite this article

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Abstract

We analyzed micro-RNAs (miRs) as possible diagnostic biomarkers for relevant comorbidities prior to and prognostic biomarkers for mortality following hematopoietic cell transplantation (HCT). A randomly selected group of patients (n = 36) were divided into low-risk (HCT-comorbidity index [HCT-CI] score of 0 and survived HCT) and high-risk (HCT-CI scores ≥ 4 and deceased after HCT) groups. There were 654 miRs tested and 19 met the pre-specified significance level of p < 0.1. In subsequent models, only eight miRs maintained statistical significance in regression models after adjusting for baseline demographic factors; miRs-374b and -454 were underexpressed, whereas miRs-142-3p, -191, -424, -590-3p, -29c, and -15b were overexpressed among high-risk patients relative to low-risk patients. Areas under the curve for these eight miRs ranged between 0.74 and 0.81, suggesting strong predictive capacity. Consideration of miRs may improve risk assessment of mortality and should be further explored in larger future prospective studies.

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Funding

This study was supported by grants DK056465, HL099993, and HL088021 from the National Institutes of Health. MLS is also supported by a Research Scholar Grant No. RSG-13-084-01-CPHPS from the American Cancer Society (ACS) and a Contract No. CE-1304-7451 from the Patient-Centered Outcome Research Institute (PCORI). We are grateful to Gary Schoch for acquisition of data. We would like to thank Bonnie Larson, Helen Crawford, and Jennifer E. Nyland for their assistance with manuscript preparation.

Author contributions

MLS, BJT-S, and MT contributed to study design; MLS collected data and obtained funding for the study; MLS and JH contributed to sample analyses; TAG performed statistical analysis; MLS, KM, JH, MAM, BJT-S, and MT contributed to analysis and interpretation of results; MLS wrote the manuscript; MLS, MAM, BJT-S, and MT edited the manuscript.

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Authors and Affiliations

  1. Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Mohamed L. Sorror, Ted A. Gooley, Jesse Hubbard, Mario A. Marcondes & Beverly J. Torok-Storb

  2. University of Washington, Seattle, WA, USA

    Mohamed L. Sorror, Ted A. Gooley, Mario A. Marcondes & Beverly J. Torok-Storb

  3. NanoString Technologies, Seattle, WA, USA

    Kirsteen H. Maclean

  4. University of Michigan, Ann Arbor, MI, USA

    Muneesh Tewari

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  1. Mohamed L. Sorror
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  2. Ted A. Gooley
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Correspondence to Mohamed L. Sorror.

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Conflict of interest

KHM is employed by NanoString Technologies, which provided the assay to determine expressions of miRs. The remaining authors declare that they have no conflict of interest.

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Sorror, M.L., Gooley, T.A., Maclean, K.H. et al. Pre-transplant expressions of microRNAs, comorbidities, and post-transplant mortality. Bone Marrow Transplant 54, 973–979 (2019). https://doi.org/10.1038/s41409-018-0352-9

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