Tumor Biology

, Volume 37, Issue 7, pp 9343–9355 | Cite as

Overexpression of annexin A4 indicates poor prognosis and promotes tumor metastasis of hepatocellular carcinoma

  • Wenwei Chen
  • Lihong Chen
  • Zhixiong Cai
  • Dong Liang
  • Bixing Zhao
  • Yongyi Zeng
  • Xiaolong Liu
  • Jingfeng Liu
Original Article

Abstract

The prognosis of hepatocellular carcinoma (HCC) after surgical resection remains unsatisfactory for the majority of HCC patients who developed early recurrence or metastasis. There is still a lack of reliable biomarkers that can be used to predict the possibility of recurrence/metastasis in HCC patients after operation. In the current study, annexin A4, a calcium-dependent phospholipid-binding protein, has been found to be significantly elevated in HCC patients with early recurrence/metastasis, and had a strong correlation with portal vein tumor thrombosis (p = 0.03) and advanced BCLC stage (p = 0.002). Cox proportional hazards regression analysis revealed that annexin A4 was an independent prognostic predictor for both early recurrence/metastasis (HR = 1.519, p = 0.032) and overall survival (HR = 1.827, p = 0.009) after surgical resection. Meanwhile, Kaplan–Meier analysis showed that Patients with high-expression levels of annexin A4 had higher recurrence rate and shorter overall survival than those with low expression (log-rank test, p < 0.001). Furthermore, in vitro studies have demonstrated that overexpression of annexin A4 facilitated HCC cell migration and invasion via regulating epithelial–mesenchymal transition (EMT). In conclusion, annexin A4 has played important roles in the progression of HCC, and might act as a potential prognostic biomarker for HCC.

Keywords

Annexin A4 Early recurrences/metastasis Epithelial–mesenchymal transition (EMT) Hepatocellular Carcinoma (HCC) Prognostic biomarker 

Notes

Acknowledgments

This work is supported by the key clinical specialty discipline construction program of Fujian, People’s Republic of China; the National Natural Science Foundation of China (Grant No. 31201008, Grant No. 31400634); the specialized Science and Technology Key Project of Fujian Province (Grant No. 2013YZ0002-3); the Science and Technology Infrastructure Construction Program of Fujian Province (Grant No. 2014Y2005); the scientific innovation project of Fujian provincial Health and Family Planning Commission (Grant No. 2014-CXB-24); the Scientific Foundation of Fuzhou City (Grant No. 2015-S-143-20).

Compliance with ethical standards

Conflict of interest

None

Supplementary material

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Wenwei Chen
    • 1
  • Lihong Chen
    • 2
    • 3
    • 4
  • Zhixiong Cai
    • 2
    • 3
  • Dong Liang
    • 2
    • 3
  • Bixing Zhao
    • 2
    • 3
  • Yongyi Zeng
    • 1
    • 2
    • 3
  • Xiaolong Liu
    • 2
    • 3
  • Jingfeng Liu
    • 1
    • 2
    • 3
  1. 1.Liver Disease Center, The First Affiliated Hospital of Fujian Medical UniversityFuzhouPeople’s Republic of China
  2. 2.The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian ProvinceMengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhouPeople’s Republic of China
  3. 3.The Liver Center of Fujian Province, Fujian Medical UniversityFuzhouPeople’s Republic of China
  4. 4.Department of PathologySchool of Basic Medical Science, Fujian Medical UniversityFuzhouPeople’s Republic of China

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