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

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Tumor Biology

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.

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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).

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    1. Liver Disease Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, People’s Republic of China

      Wenwei Chen, Yongyi Zeng & Jingfeng Liu

    2. The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Xihong Road 312, Fuzhou, 350025, Fujian Province, People’s Republic of China

      Lihong Chen, Zhixiong Cai, Dong Liang, Bixing Zhao, Yongyi Zeng, Xiaolong Liu & Jingfeng Liu

    3. The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, 350025, People’s Republic of China

      Lihong Chen, Zhixiong Cai, Dong Liang, Bixing Zhao, Yongyi Zeng, Xiaolong Liu & Jingfeng Liu

    4. Department of Pathology, School of Basic Medical Science, Fujian Medical University, Fuzhou, 350004, People’s Republic of China

      Lihong Chen

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    Wenwei Chen and Lihong Chen contributed equally to this work.

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    Chen, W., Chen, L., Cai, Z. et al. Overexpression of annexin A4 indicates poor prognosis and promotes tumor metastasis of hepatocellular carcinoma. Tumor Biol. 37, 9343–9355 (2016). https://doi.org/10.1007/s13277-016-4823-6

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