RNA-seq reveals outcome-specific gene expression of MMP7 and PCK1 in biliary atresia

Priya Ramachandran, Deepak Balamurali, J. John Peter, M. Milner Kumar, Mohamed Safwan, Mukul Vij, Mohamed Rela, Sundarasamy Mahalingam

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)5123-5130
Number of pages8
JournalMolecular Biology Reports
Volume46
Issue number5
DOIs
StatePublished - 1 Oct 2019
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2019, Springer Nature B.V.

Funding

This work was supported by grants from Department of Science & Technology, Govt. of India [VI-D&P/411/2012-2013/TDT(G)], and Indian Institute of Technology Madras [BIO/17-18/865/RFER/SMAH] to SM. The authors would like to acknowledge the contributions of Surya R., Christopher S., Rajesh Kumar R., Rajadurai K., Indu Bharath P., Munishwari V., Sneha and Saravana Kumar N. in collection and storage of patient samples immediately after KPE surgery. This work was supported by grants from Department of Science & Technology, Govt. of India [VI-D&P/411/2012-2013/TDT(G)], and Indian Institute of Technology Madras [BIO/17-18/865/RFER/SMAH] to SM. The authors would like to acknowledge the contributions of Surya R., Christopher S., Rajesh Kumar R., Rajadurai K., Indu Bharath P., Munishwari V., Sneha and Saravana Kumar N. in collection and storage of patient samples immediately after KPE surgery.

FundersFunder number
Department of Science & Technology, Govt.P/411/2012-2013/TDT(G)
Indian Institute of Technology MadrasBIO/17-18/865/RFER/SMAH
Department of Science and Technology, Government of West Bengal

    Keywords

    • Biliary atresia
    • Jaundice
    • Kasai portoenterostomy
    • Liver transplantation
    • Neonatal cholestasis
    • Next generation sequencing

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