Correlation of Circulating Human Blood RNA Biomarkers and Clinical Outcomes in an Observational Invasive Aspergillosis (IA) Trial

Ref ID: 18710

Author:

N. J. Murgolo, PhD – Fellow1, W. Ding, PhD – Principal Scientist 1, J. Li, PhD – Team Member 1, R. A. Railkar, PhD – Associate Director 2, R. L. Fox, PhD – Associate Early Clinical Development Spec. 2, C. M. Douglas, PhD – TIDV Lead 3, P. D. Mozley,

Author address:

1Merck Res. Lab., Kenilworth, NJ, 2Merck Res. Lab., North Wales, PA, 3Merck Res. Lab., West Point, PA, 4Merck Res. Lab., Rahway, NJ, 5Merck Res. Lab., Boston, MA.

Full conference title:

52nd Annual ICAAC

Date: 9 September 2014

Abstract:

Background: Developing IA therapies is hampered by difficulty in assessing early treatment response and clinical prognosis. A biomarker interposed between treatment initiation and patient outcome will aid therapy evaluation.
Methods: We examined human blood gene expression level correlation with clinical outcomes (exploratory objective) in a post-hoc assessment of a 12-week prospective, multi-center, observational clinical study (clinicaltrials.gov NCT00854607 primary objective fungal serum sugar correlation). 116 patients ≥ 16 years of age with presumptive possible, probable, or proven IA infection were enrolled and started on antifungal therapy. Those with proven or probable IA after 14 days were assessed for clinical outcomes (complete or partial response, or failure) at weeks 6 and 12 (n = 51). Blood was drawn for mRNA expression profiling at four time points across a 12-week period: baseline, weeks 2, 6, and 12.
Results: T and NK cell activation pathway genes (e.g. ZAP70, NFAT) were differentially expressed over time (outcomes correlation p=0.01). ANOVA on outcomes and time points with transcript expression data normalized to pretreatment identified a gene panel with 158 differentially expressed genes (outcomes correlation p = 1e-08). Conclusions: RNA expression profiling appears promising as a biomarker of anti-fungal drug clinical response. Prospective evaluation and validation are warranted.

Abstract Number: M-1695

Conference Poster: y

Conference Year: 2012

Link to conference website: NULL

New link: NULL

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