Research Papers:

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 and Tai-Long Pan _

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Oncotarget. 2017; 8:88951-88964. https://doi.org/10.18632/oncotarget.21627

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Pei-Wen Wang1,*, Yu-Ching Hung2,3,*, Tung-Ho Wu4,*, Mu-Hong Chen5,6, Chau-Ting Yeh7 and Tai-Long Pan3,7,8,9

1Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan

2Department of Chinese Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Kaohsiung, Taiwan

3School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, Taiwan

4Division of Cardiovascular Surgery, Veterans General Hospital, Kaohsiung, Taiwan

5Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan

6Department of Psychiatry, College of Medicine, National Yang-Ming University, Taipei, Taiwan

7Liver Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan

8Research Center for Chinese Herbal Medicine and Research Center for Food and Cosmetic Safety, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan

9Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, Taoyuan, Taiwan

*These authors have contributed equally to this work

Correspondence to:

Tai-Long Pan, email: [email protected]

Chau-Ting Yeh, email: [email protected]

Keywords: hepatic fibrosis, proteome, dimethylnitrosamine, ApoA4, network analysis

Received: July 26, 2017     Accepted: August 28, 2017     Published: October 06, 2017


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 dimethylnitrosamine-induced 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.

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