RNA-seq reveals outcome-specific gene expression of MMP7 and PCK1 in biliary atresia.
Biliary Atresia
/ genetics
Child, Preschool
Disease Progression
Female
Gene Expression Profiling
/ methods
High-Throughput Nucleotide Sequencing
Humans
Infant
Intracellular Signaling Peptides and Proteins
/ genetics
Male
Matrix Metalloproteinase 7
/ genetics
Phosphoenolpyruvate Carboxykinase (GTP)
/ genetics
Portoenterostomy, Hepatic
Prognosis
Prospective Studies
Sequence Analysis, RNA
Treatment Outcome
Up-Regulation
Exome Sequencing
Biliary atresia
Jaundice
Kasai portoenterostomy
Liver transplantation
Neonatal cholestasis
Next generation sequencing
Journal
Molecular biology reports
ISSN: 1573-4978
Titre abrégé: Mol Biol Rep
Pays: Netherlands
ID NLM: 0403234
Informations de publication
Date de publication:
Oct 2019
Oct 2019
Historique:
received:
08
05
2019
accepted:
04
07
2019
pubmed:
26
7
2019
medline:
18
2
2020
entrez:
26
7
2019
Statut:
ppublish
Résumé
The disease phenotype in biliary atresia (BA) is caused by a fibro-inflammatory process leading to destruction of cholangiocytes, obstruction of ductular pathways and eventual progression to liver cirrhosis. The first line of management is a Kasai portoenterostomy (KPE) followed by liver transplantation (LT) in some children. Several factors have been postulated to affect the outcome of KPE and/or the subsequent progression of liver disease. However, no biomarkers have been identified in the liver for BA. We aimed to address this deficit. Whole transcriptome mRNA sequencing was performed for 29 samples (25 BA and 4 Controls) to identify the candidate genes predicting the prognosis of KPE. These results were further confirmed with quantitative Realtime PCR (qPCR). Analysis from RNA-sequencing data identified matrix metalloproteinase7 (MMP7) and phosphoenolpyruvate carboxykinase (PCK1) as potential determinants of the outcome of KPE. MMP7 expression was significantly elevated in patients who failed to clear jaundice after KPE as well as in patients with End Stage Liver Disease (ESLD). In contrast, PCK1 level was upregulated in patients who had successful KPE, while there was a significant down regulation in patients who failed KPE. MMP7 and PCK1 expression patterns had an inverse relation to the outcome of KPE and hence could potentially be used as biomarkers to predict KPE outcome and disease progression, enabling clinicians to design new treatment strategies for BA.
Identifiants
pubmed: 31342296
doi: 10.1007/s11033-019-04969-3
pii: 10.1007/s11033-019-04969-3
doi:
Substances chimiques
Intracellular Signaling Peptides and Proteins
0
MMP7 protein, human
EC 3.4.24.23
Matrix Metalloproteinase 7
EC 3.4.24.23
PCK1 protein, human
EC 4.1.1.32
Phosphoenolpyruvate Carboxykinase (GTP)
EC 4.1.1.32
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
5123-5130Subventions
Organisme : Department of Science and Technology, Ministry of Science and Technology, Government of India
ID : VI-D&P/411/2012-2013/TDT(G)
Organisme : Indian Institute of Technology Madras, Chennai, India
ID : BIO/17-18/865/RFER/SMAH
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