High Expression of Metadherin in Alpha Fetoprotein Negative Hepatocellular Carcinoma Patients Following Curative Hepatectomy and Its Significance_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 LIJin-miao ¹ , HUANGZhi-min ² ,  ZHOUGui-tai ¹

1. Department of Pathology, People's Hospital of Tongcheng Country, Tongcheng 437400, Hubei Province, China;
2. Department of Hepatobiliary, People's Hospital of Tongcheng Country, Tongcheng 437400, Hubei Province, China;

Corresponding author：

ZHOUGui-tai, Email: gtzhou@sina.com

Keywords：

Hepatocellular carcinoma; Metadherin; Prognosis; Survival

DOI：

10.7507/1007-9424.20150156

Video：

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Objective To evaluate the prognosis value of oncoprotein metadherin (MTDH) in alpha fetoprotein (AFP)negative hepatocellular carcinoma (HCC) patients following curative hepatectomy. Methods The expression of MTDH protein in 152 AFP negative HCC patients underwent curative hepatectomy from 2007 to 2010 in this hospital was detected by immunohistochemical stain. Clinicopathologic data for these patients were analyzed. Survival analysis was evaluated with Kaplan-Meier method and log-rank test to compare survival difference. Cox proportional hazard model analysis was used to assess prognostic significance of MTDH in AFP negative HCC patients. Results The rate of MTDH high expression in the AFP negative HCC tissue was 60.53% (92/152). MTDH high expression was associated with tumor diameter (P=0.029), Edmondson grade (P=0.032), microvascular invasion (P=0.024), or tumor recurrence (P=0.014). Univariate and Cox proportional hazard model analysis showed that high expression of MTDH was correlated with the poor survival in AFP negative HCC patients (P=0.002, P=0.017). Conclusion MTDH is an independent predictor for survival in AFP negative HCC patients after curative hepatectomy.

Citation： LIJin-miao, HUANGZhi-min, ZHOUGui-tai. High Expression of Metadherin in Alpha Fetoprotein Negative Hepatocellular Carcinoma Patients Following Curative Hepatectomy and Its Significance. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2015, 22(5): 597-600. doi: 10.7507/1007-9424.20150156 Copy

1.	Calin GA, Ferracin M, Cimmino A, et al. A microRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med, 2005, 353(17):1793-1801.
2.	Peng SY, Chen WJ, Lai PL, et al. High alpha-fetoprotein level correlates with high stage, early recurrence and poor prognosis of hepatocellular carcinoma:Significance of hepatitis virus infection, age, p53 and beta-catenin mutations. Int J Cancer, 2004, 112(1):44-50.
3.	Xie C, Wu J, Yun J, et al. MACC1 as a prognostic biomarker for early-stage and AFP-normal hepatocellular carcinoma. PLoS One, 2013, 8(5):e64235.
4.	Lee SG, Su ZZ, Emdad L, Sarkar D et al. Astrocyte elevated gene-activates cell survival pathways through PI3K-Akt signaling. Oncogene, 2008, 27(8):1114-1121.
5.	Kang DC, Su ZZ, Sarkar D, et al. Cloning and characterization of HIV-1-inducible astrocyte elevated gene-1, AEG-1. Gene, 2005, 353(1):8-15.
6.	Yoo BK, Emdad L, Su ZZ, et al. Astrocyte elevated gene-1 regulates hepatocellular carcinoma development and progression. J Clin Invest, 2009, 119(3):465-477.
7.	Liu Y, Su ZW, Li G, et al. Increased expression of metadherin protein predicts worse disease-free and overall survival in laryngeal squamous cell carcinoma. Int J Cancer, 2013, 133(3):671-679.
8.	Liu G, Huang X, Cui X, et al. High SKIP expression is correlated with poor prognosis and cell proliferation of hepatocellular carcinoma. Med Oncol, 2013, 30(3):537.
9.	Brown DM, Ruoslahti E. Metadherin, a cell surface protein in breast tumors that mediates lung metastasis. Cancer Cell, 2004, 5(4):365-374.
10.	Huang W, Yang L, Liang S, et al. AEG-1 is a target of perifosine and is over-expressed in gastric dysplasia and cancers. Dig Dis Sci, 2013, 58(10):2873-2880.
11.	Yao Y, Gu X, Liu H, et al. Metadherin regulates proliferation and metastasis via actin cytoskeletal remodelling in non-small cell lung cancer. Br J Cancer, 2014, 111(2):355-364.
12.	Nikpour M, Emadi-Baygi M, Fischer U, et al. MTDH/AEG-1 contributes to central features of the neoplastic phenotype in bladder cancer. Urol Oncol, 2014, 32(5):670-677.
13.	Yu C, Liu Y, Tan H, et al. Metadherin regulates metastasis of squamous cell carcinoma of the head and neck via AKT signalling pathway-mediated epithelial-mesenchymal transition. Cancer Lett, 2014, 343(2):258-267.
14.	Hui AB, Bruce JP, Alajez NM, et al. Significance of dysregulated metadherin and microRNA-375 in head and neck cancer. Clin Cancer Res, 2011, 17(24):7539-7550.
15.	Zhu K, Dai Z, Pan Q, et al. Metadherin promotes hepatocellular carcinoma metastasis through induction of epithelial-mesenchymal transition. Clin Cancer Res, 2011, 17(23):7294-7302.
16.	Sarkar D. AEG-1/MTDH/LYRIC in liver cancer. Adv Cancer Res, 2013, 120:193-221.
17.	Eissa LA, Eisa NH, Ebrahim M, et al. Nitric oxide is a potential diagnostic marker for hepatocellular carcinoma. Sci Pharm, 2013, 81(3):763-775.
18.	Chan SL, Mo F, Johnson PJ, et al. Performance of serumα-fetoprotein levels in the diagnosis of hepatocellular carcinoma in patients with a hepatic mass. HPB (Oxford), 2014, 16(4):366-372.
19.	Gopal P, Yopp AC, Waljee AK, et al. Factors that affect accuracy ofα-fetoprotein test in detection of hepatocellular carcinoma in patients with cirrhosis. Clin Gastroenterol Hepatol, 2014, 12(5):870-877.
20.	Bhat M, Hassanain M, Simoneau E, et al. Magnitude of change in alpha-fetoprotein in response to transarterial chemoembolization predicts survival in patients undergoing liver transplantation for hepatocellular carcinoma. Curr Oncol, 2013, 20(5):265-272.
21.	Bruix J, Sherman M; Practice Guidelines Committee, American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma. Hepatology, 2005, 42(5):1208-1236.
22.	Omata M, Lesmana LA, Tateishi R, et al. Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma. Hepatol Int, 2010, 4(2):439-474.
23.	Fan LF, Zhao WC, Yang N, et al. Alpha-fetoprotein:the predictor of microvascular invasion in solitary small hepatocellular carcinoma and criterion for anatomic or non-anatomic hepatic resection. Hepatogastroenterology, 2013, 60(124):825-836.
24.	Singal AG, Conjeevaram HS, Volk ML, et al. Effectiveness of hepatocellular carcinoma surveillance in patients with cirrhosis. Cancer Epidemiol Biomarkers Prev, 2012, 21(5):793-799.

1. Calin GA, Ferracin M, Cimmino A, et al. A microRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med, 2005, 353(17):1793-1801.
2. Peng SY, Chen WJ, Lai PL, et al. High alpha-fetoprotein level correlates with high stage, early recurrence and poor prognosis of hepatocellular carcinoma:Significance of hepatitis virus infection, age, p53 and beta-catenin mutations. Int J Cancer, 2004, 112(1):44-50.
3. Xie C, Wu J, Yun J, et al. MACC1 as a prognostic biomarker for early-stage and AFP-normal hepatocellular carcinoma. PLoS One, 2013, 8(5):e64235.
4. Lee SG, Su ZZ, Emdad L, Sarkar D et al. Astrocyte elevated gene-activates cell survival pathways through PI3K-Akt signaling. Oncogene, 2008, 27(8):1114-1121.
5. Kang DC, Su ZZ, Sarkar D, et al. Cloning and characterization of HIV-1-inducible astrocyte elevated gene-1, AEG-1. Gene, 2005, 353(1):8-15.
6. Yoo BK, Emdad L, Su ZZ, et al. Astrocyte elevated gene-1 regulates hepatocellular carcinoma development and progression. J Clin Invest, 2009, 119(3):465-477.
7. Liu Y, Su ZW, Li G, et al. Increased expression of metadherin protein predicts worse disease-free and overall survival in laryngeal squamous cell carcinoma. Int J Cancer, 2013, 133(3):671-679.
8. Liu G, Huang X, Cui X, et al. High SKIP expression is correlated with poor prognosis and cell proliferation of hepatocellular carcinoma. Med Oncol, 2013, 30(3):537.
9. Brown DM, Ruoslahti E. Metadherin, a cell surface protein in breast tumors that mediates lung metastasis. Cancer Cell, 2004, 5(4):365-374.
10. Huang W, Yang L, Liang S, et al. AEG-1 is a target of perifosine and is over-expressed in gastric dysplasia and cancers. Dig Dis Sci, 2013, 58(10):2873-2880.
11. Yao Y, Gu X, Liu H, et al. Metadherin regulates proliferation and metastasis via actin cytoskeletal remodelling in non-small cell lung cancer. Br J Cancer, 2014, 111(2):355-364.
12. Nikpour M, Emadi-Baygi M, Fischer U, et al. MTDH/AEG-1 contributes to central features of the neoplastic phenotype in bladder cancer. Urol Oncol, 2014, 32(5):670-677.
13. Yu C, Liu Y, Tan H, et al. Metadherin regulates metastasis of squamous cell carcinoma of the head and neck via AKT signalling pathway-mediated epithelial-mesenchymal transition. Cancer Lett, 2014, 343(2):258-267.
14. Hui AB, Bruce JP, Alajez NM, et al. Significance of dysregulated metadherin and microRNA-375 in head and neck cancer. Clin Cancer Res, 2011, 17(24):7539-7550.
15. Zhu K, Dai Z, Pan Q, et al. Metadherin promotes hepatocellular carcinoma metastasis through induction of epithelial-mesenchymal transition. Clin Cancer Res, 2011, 17(23):7294-7302.
16. Sarkar D. AEG-1/MTDH/LYRIC in liver cancer. Adv Cancer Res, 2013, 120:193-221.
17. Eissa LA, Eisa NH, Ebrahim M, et al. Nitric oxide is a potential diagnostic marker for hepatocellular carcinoma. Sci Pharm, 2013, 81(3):763-775.
18. Chan SL, Mo F, Johnson PJ, et al. Performance of serumα-fetoprotein levels in the diagnosis of hepatocellular carcinoma in patients with a hepatic mass. HPB (Oxford), 2014, 16(4):366-372.
19. Gopal P, Yopp AC, Waljee AK, et al. Factors that affect accuracy ofα-fetoprotein test in detection of hepatocellular carcinoma in patients with cirrhosis. Clin Gastroenterol Hepatol, 2014, 12(5):870-877.
20. Bhat M, Hassanain M, Simoneau E, et al. Magnitude of change in alpha-fetoprotein in response to transarterial chemoembolization predicts survival in patients undergoing liver transplantation for hepatocellular carcinoma. Curr Oncol, 2013, 20(5):265-272.
21. Bruix J, Sherman M; Practice Guidelines Committee, American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma. Hepatology, 2005, 42(5):1208-1236.
22. Omata M, Lesmana LA, Tateishi R, et al. Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma. Hepatol Int, 2010, 4(2):439-474.
23. Fan LF, Zhao WC, Yang N, et al. Alpha-fetoprotein:the predictor of microvascular invasion in solitary small hepatocellular carcinoma and criterion for anatomic or non-anatomic hepatic resection. Hepatogastroenterology, 2013, 60(124):825-836.
24. Singal AG, Conjeevaram HS, Volk ML, et al. Effectiveness of hepatocellular carcinoma surveillance in patients with cirrhosis. Cancer Epidemiol Biomarkers Prev, 2012, 21(5):793-799.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

High Expression of Metadherin in Alpha Fetoprotein Negative Hepatocellular Carcinoma Patients Following Curative Hepatectomy and Its Significance

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