Proteome-based identification of apolipoprotein A-IV as an early diagnostic biomarker in liver fibrosis

Pei Wen Wang, Yu Ching Hung, Tung Ho Wu, Mu Hong Chen, Chau Ting Yeh, Tai Long Pan*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

16 Scopus citations

Abstract

Hepatic fibrosis may ultimately result in organ failure and death, a reality compounded by the fact that most drugs for liver fibrosis appear to be effective only if given as a prophylactic or early treatment. In a dimethylnitrosamineinduced liver fibrotic model, aspartate aminotransferase/alanine aminotransferase levels could not precisely distinguish the differences between the initial stage of liver fibrosis and normal control, whereas histological examination indicated that dimethylnitrosamine treatment for two weeks has resulted in hepatic fibrogenesis. Comprehensive proteomics identified 12 proteins mainly associated with the interleukin 6-stimulated inflammatory pathway. Coordinately, cytokine profiles showed that dimethylnitrosamine administration would stimulate various signaling pathways leading to liver fibrosis. Of note, apolipoprotein A4 in serum samples obtained from patients in the early stage of liver fibrosis were significantly increased compared to the healthy controls (p < 0.001) while the area under curve was 0.966. Moreover, increased apolipoprotein A4 significantly enhanced transforming growth factor beta 1-induced alpha smooth muscle actin expression. In this regard, overexpression of apolipoprotein A4 in early stage of liver fibrosis might magnify and imply the progression of hepatic fibrosis. These findings suggest that apolipoprotein A4 upregulation may correlate with hepatic fibrosis staging and that apolipoprotein A4 together with current biomarker can increase the sensitivity and specificity for the early detection of liver fibrosis in a high-throughput manner.

Original languageEnglish
Pages (from-to)88951-88964
Number of pages14
JournalOncotarget
Volume8
Issue number51
DOIs
StatePublished - 2017

Bibliographical note

Publisher Copyright:
© Wang et al.

Keywords

  • ApoA4
  • Dimethylnitrosamine
  • Hepatic fibrosis
  • Network analysis
  • Proteome

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