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Tumor Biology

, Volume 37, Issue 10, pp 14193–14203 | Cite as

Downregulation of paraoxonase 3 contributes to aggressive human hepatocellular carcinoma progression and associates with poor prognosis

  • Yuepeng Jin
  • Qiang Li
  • Junjun Qiu
  • Xiufen Zhao
  • Chunxiao Zheng
  • Shixu Lv
  • Yongyu Bai
  • Yunfeng Shan
  • Le-chi Ye
Original Article

Abstract

Paraoxonase (PON) enzymes possess antioxidant properties and protect against cardiovascular diseases. As a member of PON family, PON3 is primarily synthesized in the liver and poorly investigated. This study aimed to examine the expression of PON3 in human hepatocellular carcinoma (HCC) and investigate the clinical significance and biological function of PON3 in HCC patients. We first analyzed PON3 expression in 50 paired HCC samples (HCC tissues vs matched para-cancerous tissues) and 160 clinical HCC specimens by using immunohistochemistry (IHC). Our results showed that the expression of PON3 was downregulated in HCC and significantly associated with tumor-node-metastasis (TNM) stage, tumor size, and tumor number. Kaplan-Meier survival and Cox regression analyses showed that PON3 was an independent prognostic factor for overall survival (OS) and time to recurrence (TTR). Finally, we aimed to reveal the biological function of PON3 in HCC growth and metastasis, and our results showed that overexpression of PON3 potently inhibited growth and metastasis of HCC. Collectively, our study demonstrated that PON3 exhibited tumor-suppressive effects toward HCC and it might serve as a novel prognostic marker in HCC.

Keywords

Paraoxonase 3 Hepatocellular carcinoma Prognosis Growth Metastasis 

Notes

Acknowledgments

This study was supported by grants from Zhejiang Provincial Natural Science Foundation of China (nos. LY12H03006 and LY15H160058) and the National Natural Science Foundation of China (no. 81572291).

Compliance with ethical standards

Conflicts of interest

None

Supplementary material

13277_2016_5247_MOESM1_ESM.jpg (160 kb)
Supplementary Figure 1 Analysis for protein levels of PON3 in HCC cell lines. Protein levels of PON3 were determined by Western Blot in six HCC cell lines and one immortalized liver cell line. (JPG 159 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Yuepeng Jin
    • 1
  • Qiang Li
    • 2
  • Junjun Qiu
    • 3
  • Xiufen Zhao
    • 1
  • Chunxiao Zheng
    • 1
  • Shixu Lv
    • 3
  • Yongyu Bai
    • 2
  • Yunfeng Shan
    • 1
  • Le-chi Ye
    • 4
  1. 1.Department of General Surgery, The First Affiliated HospitalWenzhou Medical UniversityWenzhouChina
  2. 2.Wenzhou Medical UniversityWenzhouChina
  3. 3.Department of Gynecology, Obstetrics and Gynecology HospitalFudan UniversityShanghaiChina
  4. 4.Department of Oncological SurgeryThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina

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