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Tumor Biology
Published in: Tumor Biology 12/2015

01-12-2015 | Research Article

Up-regulation of annexin A2 expression predicates advanced clinicopathological features and poor prognosis in hepatocellular carcinoma

Authors: Haijian Zhang, Min Yao, Wei Wu, Liwei Qiu, Wenli Sai, Junling Yang, Wenjie Zheng, Jianfei Huang, Dengfu Yao

Published in: Tumor Biology | Issue 12/2015

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Abstract

Hepatic annexin A2 (ANXA2) orchestrates multiple biologic processes and clinical symptoms and plays a key role in development, metastasis, and drug resistance of lethal hepatocellular carcinoma (HCC). However, the prognostic significance of ANXA2 for HCC has not been elucidated up to now. In this study, ANXA2 was frequently found to be up-regulated in HCC tissues compared with benign liver disease (BLD) tissues, which was consistent with the results in serum samples and tissue specimens of patients with HCC. Furthermore, ANXA2 expression was significantly correlated with differentiated degree, intrahepatic metastasis, portal vein thrombus, and tumor node metastasis (TNM) staging. More importantly, increased ANXA2 level was first confirmed to be closely associated with shortened overall survival of HCC (χ 2 = 12.872, P = 0.005) and identified as an independent prognostic factor (hazard ratio 1.338, 95 % confidence interval (CI) 1.013 ~ 1.766, P = 0.040), suggesting that ANXA2 up-regulation might represent an acquired metastasis phenotype of HCC, help to screen out high-risk population for HCC, or more effectively treat a subset of postsurgical HCC patients positive for ANXA2.
Literature
1.
2.
Nguyen VT, Law MG, Dore GJ. Hepatitis B-related hepatocellular carcinoma: epidemiological characteristics and disease burden. J Viral Hepat. 2009;16(7):453–63.CrossRefPubMed
3.
Ichikawa T, Sano K, Morisaka H. Diagnosis of pathologically early HCC with EOB-MRI: experiences and current consensus. Liver Cancer. 2014;3(2):97–107.CrossRefPubMedPubMedCentral
4.
Shoreibah MG, Bloomer JR, McGuire BM, Massoud OI. Surveillance for hepatocellular carcinoma: evidence, guidelines and utilization. Am J Med Sci. 2014;347(5):415–9.CrossRefPubMed
5.
Sun H, Zhu MS, Wu WR, Shi XD, Xu LB. Role of anti-angiogenesis therapy in the management of hepatocellular carcinoma: the jury is still out. World J Hepatol. 2014;6(12):830–5.CrossRefPubMedPubMedCentral
6.
Wang CY, Lin CF. Annexin A2: its molecular regulation and cellular expression in cancer development. Dis Markers. 2014;2014:308976.PubMedPubMedCentral
7.
Chaiteerakij R, Addissie BD and Roberts LR. Update on biomarkers of hepatocellular carcinoma. Clin Gastroenterol Hepatol. 2013.
8.
9.
Jour G, Gullet A, Liu M, Hoch BL. Prognostic relevance of Federation Nationale des Centres de Lutte Contre le Cancer grade and MDM2 amplification levels in dedifferentiated liposarcoma: a study of 50 cases. Mod Pathol. 2015;28(1):37–47.CrossRefPubMed
10.
Llovet JM, Bruix J. Prospective validation of the Cancer of the Liver Italian Program (CLIP) score: a new prognostic system for patients with cirrhosis and hepatocellular carcinoma. Hepatology. 2000;32(3):679–80.CrossRefPubMed
11.
Luo CH, Liu QQ, Zhang PF, Li MY, Chen ZC, Liu YF. Prognostic significance of annexin II expression in non-small cell lung cancer. Clin Transl Oncol. 2013;15(11):938–46.CrossRefPubMed
12.
Yang T, Peng H, Wang J, Yang J, Nice EC, Xie K, et al. Prognostic and diagnostic significance of annexin A2 in colorectal cancer. Colorectal Dis. 2013;15(7):e373–81.CrossRefPubMed
13.
Waisman DM. Annexin II, tetramer: structure and function. Mol Cell Biochem. 1995;149–150:301–22.CrossRefPubMed
14.
Hedhli N, Falcone DJ, Huang B, Cesarman-Maus G, Kraemer R, Zhai H, et al. The annexin A2/S100A10 system in health and disease: emerging paradigms. J Biomed Biotechnol. 2012;2012:406273.CrossRefPubMedPubMedCentral
15.
Vedeler A, Hollas H, Grindheim AK, Raddum AM. Multiple roles of annexin A2 in post-transcriptional regulation of gene expression. Curr Protein Pept Sci. 2012;13(4):401–12.CrossRefPubMed
16.
Mohammad HS, Kurokohchi K, Yoneyama H, Tokuda M, Morishita A, Jian G, et al. Annexin A2 expression and phosphorylation are up-regulated in hepatocellular carcinoma. Int J Oncol. 2008;33(6):1157–63.PubMed
17.
Gao PJ, Shi Y, Gao YH, Liu YW, Tan Y. The receptor for beta(2)GP I on membrane of hepatocellular carcinoma cell line SMMC-7721 is annexin II. World J Gastroenterol. 2007;13(24):3364–8.CrossRefPubMedPubMedCentral
18.
Zhang HJ, Yao DF, Yao M, Huang H, Wu W, Yan MJ, et al. Expression characteristics and diagnostic value of annexin A2 in hepatocellular carcinoma. World J Gastroenterol. 2012;18(41):5897–904.CrossRefPubMedPubMedCentral
19.
Sun Y, Gao G, Cai J, Wang Y, Qu X, He L, et al. Annexin A2 is a discriminative serological candidate in early hepatocellular carcinoma. Carcinogenesis. 2013;34(3):595–604.CrossRefPubMed
20.
Zhao P, Zhang W, Tang J, Ma XK, Dai JY, Li Y, et al. Annexin II promotes invasion and migration of human hepatocellular carcinoma cells in vitro via its interaction with HAb18G/CD147. Cancer Sci. 2010;101(2):387–95.CrossRefPubMed
21.
Zhang W, Zhao P, Xu XL, Cai L, Song ZS, Cao DY, et al. Annexin A2 promotes the migration and invasion of human hepatocellular carcinoma cells in vitro by regulating the shedding of CD147-harboring microvesicles from tumor cells. PLoS One. 2013;8(8), e67268.CrossRefPubMedPubMedCentral
22.
Wang C, Guo Y, Wang J, Min Z. Annexin A2 knockdown inhibits hepatoma cell growth and sensitizes hepatoma cells to 5-fluorouracil by regulating betacatenin and cyclin D1 expression. Mol Med Rep. 2015;11(3):2147–52.PubMed
23.
Ministry of Health of the People’s Republic of C. Updated standards for the diagnosis and treatment of primary liver cancer. Zhonghua Gan Zang Bing Za Zhi. 2012;20(6):419–26.
24.
o Y. [Management of clinical diagnosis, and antiviral therapy for HBV-related cirrhosis]. Zhonghua Gan Zang Bing Za Zhi. 2014;22(5):327-335.
25.
M PN. World Medical Association publishes the Revised Declaration of Helsinki. Natl Med J India. 2014;27(1):56.PubMed
26.
Luo RZ, Cai PQ, Li M, Fu J, Zhang ZY, Chen JW, et al. Decreased expression of PTPN12 correlates with tumor recurrence and poor survival of patients with hepatocellular carcinoma. PLoS One. 2014;9(1), e85592.CrossRefPubMedPubMedCentral
27.
Zhang HJ, Yao DF, Yao M, Huang H, Wang L, Yan MJ, et al. Annexin A2 silencing inhibits invasion, migration, and tumorigenic potential of hepatoma cells. World J Gastroenterol. 2013;19(24):3792–801.CrossRefPubMedPubMedCentral
28.
Wang Q, Ni Q, Wang X, Zhu H, Wang Z, Huang J. High expression of RAB27A and TP53 in pancreatic cancer predicts poor survival. Med Oncol. 2015;32(1):372.CrossRefPubMed
29.
Breuhahn K, Schirmacher P. Reactivation of the insulin-like growth factor-II signaling pathway in human hepatocellular carcinoma. World J Gastroenterol. 2008;14(11):1690–8.CrossRefPubMedPubMedCentral
30.
31.
Zhang X, Liu S, Guo C, Zong J, Sun MZ. The association of annexin A2 and cancers. Clin Transl Oncol. 2012;14(9):634–40.CrossRefPubMed
32.
Lokman NA, Ween MP, Oehler MK, Ricciardelli C. The role of annexin A2 in tumorigenesis and cancer progression. Cancer Microenviron. 2011;4(2):199–208.CrossRefPubMedPubMedCentral
33.
Liu Z, Ling Q, Wang J, Xie H, Xu X, Zheng S. Annexin A2 is not a good biomarker for hepatocellular carcinoma in cirrhosis. Oncol Lett. 2013;6(1):125–9.PubMedPubMedCentral
34.
Longerich T, Haller MT, Mogler C, Aulmann S, Lohmann V, Schirmacher P, et al. Annexin A2 as a differential diagnostic marker of hepatocellular tumors. Pathol Res Pract. 2011;207(1):8–14.CrossRefPubMed
35.
Sharma M, Ownbey RT, Sharma MC. Breast cancer cell surface annexin II induces cell migration and neoangiogenesis via tPA dependent plasmin generation. Exp Mol Pathol. 2010;88(2):278–86.CrossRefPubMed
36.
Nedjadi T, Kitteringham N, Campbell F, Jenkins RE, Park BK, Navarro P, et al. S100A6 binds to annexin 2 in pancreatic cancer cells and promotes pancreatic cancer cell motility. Br J Cancer. 2009;101(7):1145–54.CrossRefPubMedPubMedCentral
37.
Zhao P, Zhang W, Wang SJ, Yu XL, Tang J, Huang W, et al. HAb18G/CD147 promotes cell motility by regulating annexin II-activated RhoA and Rac1 signaling pathways in hepatocellular carcinoma cells. Hepatology. 2011;54(6):2012–24.CrossRefPubMed
38.
de Graauw M, Cao L, Winkel L, van Miltenburg MH, le Devedec SE, Klop M, et al. Annexin A2 depletion delays EGFR endocytic trafficking via cofilin activation and enhances EGFR signaling and metastasis formation. Oncogene. 2014;33(20):2610–9.CrossRefPubMed
39.
Emoto K, Sawada H, Yamada Y, Fujimoto H, Takahama Y, Ueno M, et al. Annexin II overexpression is correlated with poor prognosis in human gastric carcinoma. Anticancer Res. 2001;21(2B):1339–45.PubMed
40.
Zimmermann U, Woenckhaus C, Pietschmann S, Junker H, Maile S, Schultz K, et al. Expression of annexin II in conventional renal cell carcinoma is correlated with Fuhrman grade and clinical outcome. Virchows Arch. 2004;445(4):368–74.CrossRefPubMed
41.
Jia JW, Li KL, Wu JX, Guo SL. Clinical significance of annexin II expression in human non-small cell lung cancer. Tumour Biol. 2013;34(3):1767–71.CrossRefPubMed
42.
Ma RL, Shen LY and Chen KN. Coexpression of ANXA2, SOD2 and HOXA13 predicts poor prognosis of esophageal squamous cell carcinoma. Oncol Rep. 2014;PMID: 24626613.
43.
Zhang Q, Zhao Z, Ma Y, Wang H, Ma J, He X, et al. Combined expression of S100A4 and Annexin A2 predicts disease progression and overall survival in patients with urothelial carcinoma. Urol Oncol. 2014;32(6):798–805.CrossRefPubMed
44.
Seckinger A, Meissner T, Moreaux J, Depeweg D, Hillengass J, Hose K, et al. Clinical and prognostic role of annexin A2 in multiple myeloma. Blood. 2012;120(5):1087–94.CrossRefPubMed
45.
Alonso-Alconada L, Santacana M, Garcia-Sanz P, Muinelo-Romay L, Colas E, Mirantes C, Monge M, Cueva J, Oliva E, Soslow RA, Lopez MA, Palacios J, Prat J, Valls J, Krakstad C, Salvesen H, Gil-Moreno A, Lopez-Lopez R, Dolcet X, Moreno-Bueno G, Reventos J, Matias-Guiu X and Abal M. Annexin-A2 as predictor biomarker of recurrent disease in endometrial cancer. Int J Cancer. 2014;PMID: 25219463.
46.
Takano S, Togawa A, Yoshitomi H, Shida T, Kimura F, Shimizu H, et al. Annexin II overexpression predicts rapid recurrence after surgery in pancreatic cancer patients undergoing gemcitabine-adjuvant chemotherapy. Ann Surg Oncol. 2008;15(11):3157–68.CrossRefPubMed
47.
Ding T, Yang L, Wang Y, Yuan J, Chen T, Cai X. Down-regulation of annexin II in prostate cancer is associated with Gleason score, recurrence, metastasis and poor prognosis. Mol Med Rep. 2010;3(5):781–7.PubMed
48.
Rodrigo JP, Lequerica-Fernandez P, Rosado P, Allonca E, Garcia-Pedrero JM, de Vicente JC. Clinical significance of annexin A2 downregulation in oral squamous cell carcinoma. Head Neck. 2011;33(12):1708–14.CrossRefPubMed
49.
Liu X, Ma D, Jing X, Wang B, Yang W, Qiu W. Overexpression of ANXA2 predicts adverse outcomes of patients with malignant tumors: a systematic review and meta-analysis. Med Oncol. 2015;32(1):392.CrossRefPubMed
Metadata
Title
Up-regulation of annexin A2 expression predicates advanced clinicopathological features and poor prognosis in hepatocellular carcinoma
Authors
Haijian Zhang
Min Yao
Wei Wu
Liwei Qiu
Wenli Sai
Junling Yang
Wenjie Zheng
Jianfei Huang
Dengfu Yao
Publication date
01-12-2015
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 12/2015
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-3678-6

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