Overexpression of annexin A4 indicates poor prognosis and promotes tumor metastasis of hepatocellular carcinoma
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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.
KeywordsAnnexin A4 Early recurrences/metastasis Epithelial–mesenchymal transition (EMT) Hepatocellular Carcinoma (HCC) Prognostic biomarker
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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- 9.Ortiz-Zapater E, Peiró S, Roda O, Corominas JM, Aguilar S, Ampurdanés C, et al. Tissue plasminogen activator induces pancreatic cancer cell proliferation by a non-catalytic mechanism that requires extracellular signal-regulated kinase 1/2 activation through epidermal growth factor receptor and annexin A2. Am J Pathol. 2007;170(5):1573–84.CrossRefPubMedPubMedCentralGoogle Scholar
- 17.Liu S, Sun MZ, Tang JW, Wang Z, Sun C, Greenaway FT. High-performance liquid chromatography/nano-electrospray ionization tandem mass spectrometry, two-dimensional difference in-gel electrophoresis and gene microarray identification of lymphatic metastasis-associated biomarkers. Rapid Commun Mass Spectrom. 2008;22(20):3172–8.CrossRefPubMedGoogle Scholar
- 18.Liu S-H, Lin C-Y, Peng S-Y, Jeng Y-M, Pan H-W, Lai P-L, et al. Down-regulation of annexin A10 in hepatocellular carcinoma is associated with vascular invasion, early recurrence, and poor prognosis in synergy with p53 mutation. Am J Pathol. 2002;160(5):1831–7.CrossRefPubMedPubMedCentralGoogle Scholar
- 23.Shen J, Person MD, Zhu J, Abbruzzese JL, Li D. Protein expression profiles in pancreatic adenocarcinoma compared with normal pancreatic tissue and tissue affected by pancreatitis as detected by two-dimensional gel electrophoresis and mass spectrometry. Cancer Res. 2004;64(24):9018–26.CrossRefPubMedGoogle Scholar
- 35.Mozos A, Sole M, Miquel R, Petit A, Nadal A, Fernández PL. Usefulness and limitations of alpha-methylacyl-CoA racemase expression in the hepatobiliary system and pancreas: a wide tissue microarray analysis of normal and neoplastic epithelia. Anal Quant Cytol Histol. 2010;32(5):261–8.PubMedGoogle Scholar
- 36.Toyama A, Suzuki A, Shimada T, Aoki C, Aoki Y, Umino Y, et al. Proteomic characterization of ovarian cancers identifying annexin-A4, phosphoserine aminotransferase, cellular retinoic acid-binding protein 2, and serpin B5 as histology-specific biomarkers. Cancer Sci. 2012;103(4):747–55.CrossRefPubMedGoogle Scholar
- 39.Huang X, Zeng Y, Xing X, Zeng J, Gao Y, Cai Z, et al. Quantitative proteomics analysis of early recurrence/metastasis of huge hepatocellular carcinoma following radical resection. Proc Natl Acad Sci U S A. 2014;12:22.Google Scholar