Pre-treatment differential correlation of gene expression and response to topical steroids in eosinophilic esophagitis.

Autor: Dellon ES; Department of Medicine, Division of Gastroenterology and Hepatology, Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, NC, USA., Tsai YS; Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.; Department of Medicine, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA., Coffey AR; Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.; Department of Medicine, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA., Bodwin K; Department of Statistics and Operations Research, University of North Carolina, Chapel Hill, NC, USA.; Statistics Department, Cal Poly, Obispo, CA, USA., Sninsky JA; Department of Medicine, Division of Gastroenterology and Hepatology, Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, NC, USA., Mosso CN; Department of Statistics and Operations Research, University of North Carolina, Chapel Hill, NC, USA., He TM; Department of Statistics and Operations Research, University of North Carolina, Chapel Hill, NC, USA., O'Connor KA; Department of Statistics and Operations Research, University of North Carolina, Chapel Hill, NC, USA., Selitsky SR; Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.; Department of Medicine, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA., Nobel AB; Department of Statistics and Operations Research, University of North Carolina, Chapel Hill, NC, USA., Parker JS; Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
Jazyk: angličtina
Zdroj: Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus [Dis Esophagus] 2023 Mar 30; Vol. 36 (4).
DOI: 10.1093/dote/doac071
Abstrakt: Few predictors of response to topical corticosteroid (tCS) treatment have been identified in eosinophilic esophagitis (EoE). We aimed to determine whether baseline gene expression predicts histologic response to tCS treatment for EoE. We analyzed prospectively collected samples from incident EoE cases who were treated with tCS for 8 weeks in a development cohort (prospective study) or in an independent validation cohort (clinical trial). Whole transcriptome RNA expression was determined from a baseline (pre-treatment) RNA-later preserved esophageal biopsy. Baseline expression was compared between histologic responders (<15 eos/hpf) and non-responders (≥15 eos/hpf), and differential correlation was used to assess baseline gene expression by response status. In 87 EoE cases analyzed in the development set, there were no differentially expressed genes associated with treatment response (at false discovery rate = 0.1). However, differential correlation identified a module of 22 genes with statistically significantly high pairwise correlation in non-responders (mean correlation coefficient = 0.7) compared to low correlation in responders (coefficient = 0.3). When this 22-gene module was applied to the 89 EoE cases in the independent cohort, it was not validated to predict tCS response at the 15 eos/hpf threshold (mean correlation coefficient = 0.32 in responders and 0.25 in nonresponders). Exploration of other thresholds also did not validate any modules. Though we identified a 22 gene differential correlation module measured pre-treatment that was strongly associated with subsequent histologic response to tCS in EoE, this was not validated in an independent population. Alternative methods to predict steroid response should be explored.
(© The Author(s) 2022. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze: MEDLINE
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