Browse by author
Lookup NU author(s): Kile Green, Dr Laura Jopson, Dr Ben Barron-Millar, Barbara Innes, Sarah Pagan, Dr Dina Tiniakos, Dr Jess Dyson, Professor Muzlifah Haniffa, Dr Venetia BigleyORCiD, Professor David Jones, Dr John Brain, Dr Lucy Walker
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2016 High-risk primary biliary cholangitis (PBC), defined by inadequate response at one year to Ursodeoxycholic acid (UDCA), is associated with disease progression and liver transplantation. Stratifying high-risk patients early would facilitate improved approaches to care. Using long-term follow-up data to define risk at presentation, 6 high-risk PBC patients and 8 low-risk patients were identified from biopsy, transplant and biochemical archival records. Formalin-fixed paraffin-embedded (FFPE) liver biopsies taken at presentation were graded (Scheuer and Nakanuma scoring) and gene expression analysed using the NanoString® nCounter PanCancer Immunity 770-gene panel. Principle component analysis (PCA) demonstrated discrete gene expression clustering between controls and high- and low-risk PBC. High-risk PBC was characterised by up-regulation of genes linked to T-cell activation and apoptosis, INF-γ signalling and leukocyte migration and down-regulation of those linked to the complement pathway. CDKN1a, up-regulated in high-risk PBC, correlated with significantly increased expression of its gene product, the senescence marker p21WAF1/Cip, by biliary epithelial cells. Our findings suggest high- and low-risk PBC are biologically different from disease outset and senescence an early feature in high-risk disease. Identification of a high-risk ‘signal’ early from standard FFPE tissue sections has clear clinical utility allowing for patient stratification and second-line therapeutic intervention.
Author(s): Hardie C, Green K, Jopson L, Millar B, Innes B, Pagan S, Tiniakos D, Dyson J, Haniffa M, Bigley V, Jones DE, Brain J, Walker LJ
Publication type: Article
Publication status: Published
Journal: EBioMedicine
Year: 2016
Volume: 14
Pages: 65-73
Print publication date: 01/12/2016
Online publication date: 21/11/2016
Acceptance date: 16/11/2016
Date deposited: 21/04/2017
ISSN (electronic): 2352-3964
Publisher: Elsevier B.V.
URL: https://doi.org/10.1016/j.ebiom.2016.11.021
DOI: 10.1016/j.ebiom.2016.11.021
PubMed id: 27913155
Altmetrics provided by Altmetric
