Expression of Metaherin and Its Clinical Significance for Hepatitis B Related Hepatocellular Carcinoma_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 OUQin ¹ , ZHAOZong-bin ² , WANGGeng ² ,  LIWen-fang ²

1. Department of Virus and Tumor Research Center, Hubei Medical University, Shiyan 442000, Hubei Province, China;
2. Department of General Surgery, Affiliated Taihe Hospital of Hubei Medical University, Shiyan 442000, Hubei Province, China;

Corresponding author：

LIWen-fang, Email: 2671422764@qq.com

Keywords：

Metaherin; Hepatitis B related hepatocellular carcinoma; Pericarcinoma tissue; Prognosis

DOI：

10.7507/1007-9424.20150081

Video：

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Objective To explore expressions of the metaherin (MTDH) mRNA and its protein in hepatitis B related hepatocellular carcinoma tissues and its clinical significance. Methods Seventy two tissues of patients with hepa-titis B related hepatocellular carcinoma who were treated in Affiliated Taihe Hospital of Hubei Medical University from Jul. 2012 to Oct. 2013 were collected retrospectively. Quantitative PCR (Q-PCR) and Western blot methods were used to detect the expression levels of MTDH mRNA and its protein in 10 cases of hepatitis B related hepatocellular carcinoma tissues and pericarcinoma tissues. Besides, immunohistochemistry was used to determine the expression of MTDH protein in 72 cases of hepatocellular carcinoma tissues, then the relationship of expression of MTDH protein and clinico-pathological features was explored. Results The expression levels of MTDH mRNA and its protein in hepatocellular carcinoma tissues were both higher than those of pericarcinoma tissues (8.50±0.84 vs. 4.55±0.81, t=10.797, P=0.000; 0.65± 0.24 vs. 0.25±0.16,t=6.375, P=0.013). The MTDH protein was positively expressed in 42 cases (58.3%) and negatively expressed in 30 cases (41.7%) of hepatocellular carcinoma tissues. The results of logistic regression showed that,MTHD protein was up-regulated in patients with category Ⅲ of Edmondson grade (OR=4.783, 95% CI:2.663-11.918, P=0.020), microvascular invasion (OR=37.790, 95% CI:2.227-99.434, P=0.005), and lymph node metastasis (OR=7.332, 95% CI:3.325-30.669, P=0.023). Conclusion Expressions of MTDH mRNA and its protein are both higher in hepatitis B related hepatocellular carcinoma tissue, which are correlated with poor prognosis.

Citation： OUQin, ZHAOZong-bin, WANGGeng, LIWen-fang. Expression of Metaherin and Its Clinical Significance for Hepatitis B Related Hepatocellular Carcinoma. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2015, 22(3): 301-306. doi: 10.7507/1007-9424.20150081 Copy

1.	Scaggiante B, Kazemi M, Pozzato G, et al. Novel hepatocellular carcinoma molecules with prognostic and therapeutic potentials. World J Gastroenterol, 2014, 20(5):1268-1288.
2.	Kim HY, Park JW. Clinical trials of combined molecular targeted therapy and locoregional therapy in hepatocellular carcinoma:past, present, and future. Liver Cancer, 2014, 3(1):9-17.
3.	Vu TH, Nguyen AH, Hoffman AR. Loss of IGF2 imprinting is associated with abrogation of long-range intrachromosomal interactions in human cancer cells. Hum Mol Genet, 2010, 19(5):901-919.
4.	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.
5.	Hu G, Wei Y, Kang Y. The multifaceted role of MTDH/AEG-1 in cancer progression. Clin Cancer Res, 2009, 15(18):5615-5620.
6.	Wang L, Liu Z, Ma D, et al. SU6668 suppresses proliferation of triple negative breast cancer cells through down-regulating MTDH expression. Cancer Cell Int, 2013, 13(1):88.
7.	Sun W, Fan YZ, Xi H, et al. Astrocyte elevated gene-1 overexpre-ssion in human primary gallbladder carcinomas:an unfavorable and independent prognostic factor. Oncol Rep, 2011, 26(5):1133-1142.
8.	刘凯歌, 高红艳, 赵慧, 等. HBx和VEGF与乙肝相关性肝癌组织血管生成及转移的关系. 吉林大学学报:医学版, 2010, 36(2):372-375.
9.	Zhou L, Rui JA, Ye DX, et al. Edmondson-steiner grading increases the predictive efficiency of TNM staging for long-term survival of patients with hepatocellular carcinoma after curative resection. World J Surg, 2008, 32(8):1748-1756.
10.	Trovato MA, Pesce A, Sofia M, et al. Is BCLC algorithm useful inclinical practice? Study on 164 HCC patients. Hepatogastroentero-logy, 2013, 60(127):1742-1745.
11.	Ahn S, Hyeon J, Park CK. Metadherin is a prognostic predictor of hepatocellular carcinoma after curative hepatectomy. Gut Liver, 2013, 7(2):206-212.
12.	Inoue M, Takahashi Y, Fujii T, et al. Significance of downregulation of liver fatty acid-binding protein in hepatocellular carcinoma. World J Gastroenterol, 2014, 20(46):17541-17551.
13.	Lee JM, Park JW, Choi BI. 2014 KLCSG-NCC Korea Practice Guidelines for the management of hepatocellular carcinoma:HCC diagnostic algorithm. Dig Dis, 2014, 32(6):764-777.
14.	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.
15.	Park SH, Lim JS, Lim SY, et al. Hepatitis C virus Core protein stimulates cell growth by down-regulating p16 expression via DNA methylation. Cancer Lett, 2011, 310(1):61-68.
16.	刘凯歌, 许刚柱, 姚杨, 等. HBx和CEACAM1在乙肝相关性肝癌中的表达及意义. 细胞与分子免疫学杂志, 2012, 28(4):410-412.
17.	Perz JF, Armstrong GL, Farrington LA, et al. The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J Hepatol, 2006, 45(4):529-538.
18.	Wu Y, Gan Y, Gao FM, et al. Novel natural mutations in the hepatitis B virus reverse transcriptase domain associated with hepatocellular carcinoma. PLoS One, 2014, 9(5):e94864.
19.	Kawanaka M, Nishino K, Nakamura J, et al. Quantitative levels of hepatitis B virus DNA and surface antigen and the risk of hepatocellular carcinoma in patients with hepatitis B receiving long-term nucleos(t)ide analogue therapy. Liver Cancer, 2014, 3(1):41-52.
20.	胡帅, 俞悦, 高云, 等. IMP3与IGF2在乙肝相关性肝癌组织中表达及与临床病理特征的关系. 南京医科大学学报:自然科学版, 2014, 13(5):568-573.
21.	党珊, 陈谱, 张冰斐, 等. 乙肝相关性肝癌患者中Foxp3启动子区甲基化及其表达的研究. 陕西医学杂志, 2014, 43(2):131-133.
22.	Xu C, Zhou WC, Wang YM, et al. Hepatitis B virus-induced hepatocellular carcinoma. Cancer Lett, 2014, 345(2):216-222.
23.	Li X, Kong X, Huo Q, et al. Metadherin enhances the invasiveness of breast cancer cells by inducing epithelial to mesenchymal transition. Cancer Sci, 2011, 102(6):1151-1157.
24.	Liu K, Guo L, Miao L, et al. Ursolic acid inhibits epithelial-mesenchymal transition by suppressing the expression of astrocyte-elevated gene-1 in human nonsmall cell lung cancer A549 cells. Anticancer Drugs, 2013, 24(5):494-503.
25.	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.
26.	Gong Z, Liu W, You N, et al. Prognostic significance of metadherin overexpression in hepatitis B virus-related hepatocellular carcinoma.Oncol Rep, 2012, 27(6):2073-2079.
27.	Lee CW, Kuo WL, Yu MC, et al. The expression of cytokeratin 19 in lymph nodes was a poor prognostic factor for hepatocellular carcinoma after hepatic resection. World J Surg Oncol, 2013, 11(1):136.

1. Scaggiante B, Kazemi M, Pozzato G, et al. Novel hepatocellular carcinoma molecules with prognostic and therapeutic potentials. World J Gastroenterol, 2014, 20(5):1268-1288.
2. Kim HY, Park JW. Clinical trials of combined molecular targeted therapy and locoregional therapy in hepatocellular carcinoma:past, present, and future. Liver Cancer, 2014, 3(1):9-17.
3. Vu TH, Nguyen AH, Hoffman AR. Loss of IGF2 imprinting is associated with abrogation of long-range intrachromosomal interactions in human cancer cells. Hum Mol Genet, 2010, 19(5):901-919.
4. 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.
5. Hu G, Wei Y, Kang Y. The multifaceted role of MTDH/AEG-1 in cancer progression. Clin Cancer Res, 2009, 15(18):5615-5620.
6. Wang L, Liu Z, Ma D, et al. SU6668 suppresses proliferation of triple negative breast cancer cells through down-regulating MTDH expression. Cancer Cell Int, 2013, 13(1):88.
7. Sun W, Fan YZ, Xi H, et al. Astrocyte elevated gene-1 overexpre-ssion in human primary gallbladder carcinomas:an unfavorable and independent prognostic factor. Oncol Rep, 2011, 26(5):1133-1142.
8. 刘凯歌, 高红艳, 赵慧, 等. HBx和VEGF与乙肝相关性肝癌组织血管生成及转移的关系. 吉林大学学报:医学版, 2010, 36(2):372-375.
9. Zhou L, Rui JA, Ye DX, et al. Edmondson-steiner grading increases the predictive efficiency of TNM staging for long-term survival of patients with hepatocellular carcinoma after curative resection. World J Surg, 2008, 32(8):1748-1756.
10. Trovato MA, Pesce A, Sofia M, et al. Is BCLC algorithm useful inclinical practice? Study on 164 HCC patients. Hepatogastroentero-logy, 2013, 60(127):1742-1745.
11. Ahn S, Hyeon J, Park CK. Metadherin is a prognostic predictor of hepatocellular carcinoma after curative hepatectomy. Gut Liver, 2013, 7(2):206-212.
12. Inoue M, Takahashi Y, Fujii T, et al. Significance of downregulation of liver fatty acid-binding protein in hepatocellular carcinoma. World J Gastroenterol, 2014, 20(46):17541-17551.
13. Lee JM, Park JW, Choi BI. 2014 KLCSG-NCC Korea Practice Guidelines for the management of hepatocellular carcinoma:HCC diagnostic algorithm. Dig Dis, 2014, 32(6):764-777.
14. 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.
15. Park SH, Lim JS, Lim SY, et al. Hepatitis C virus Core protein stimulates cell growth by down-regulating p16 expression via DNA methylation. Cancer Lett, 2011, 310(1):61-68.
16. 刘凯歌, 许刚柱, 姚杨, 等. HBx和CEACAM1在乙肝相关性肝癌中的表达及意义. 细胞与分子免疫学杂志, 2012, 28(4):410-412.
17. Perz JF, Armstrong GL, Farrington LA, et al. The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J Hepatol, 2006, 45(4):529-538.
18. Wu Y, Gan Y, Gao FM, et al. Novel natural mutations in the hepatitis B virus reverse transcriptase domain associated with hepatocellular carcinoma. PLoS One, 2014, 9(5):e94864.
19. Kawanaka M, Nishino K, Nakamura J, et al. Quantitative levels of hepatitis B virus DNA and surface antigen and the risk of hepatocellular carcinoma in patients with hepatitis B receiving long-term nucleos(t)ide analogue therapy. Liver Cancer, 2014, 3(1):41-52.
20. 胡帅, 俞悦, 高云, 等. IMP3与IGF2在乙肝相关性肝癌组织中表达及与临床病理特征的关系. 南京医科大学学报:自然科学版, 2014, 13(5):568-573.
21. 党珊, 陈谱, 张冰斐, 等. 乙肝相关性肝癌患者中Foxp3启动子区甲基化及其表达的研究. 陕西医学杂志, 2014, 43(2):131-133.
22. Xu C, Zhou WC, Wang YM, et al. Hepatitis B virus-induced hepatocellular carcinoma. Cancer Lett, 2014, 345(2):216-222.
23. Li X, Kong X, Huo Q, et al. Metadherin enhances the invasiveness of breast cancer cells by inducing epithelial to mesenchymal transition. Cancer Sci, 2011, 102(6):1151-1157.
24. Liu K, Guo L, Miao L, et al. Ursolic acid inhibits epithelial-mesenchymal transition by suppressing the expression of astrocyte-elevated gene-1 in human nonsmall cell lung cancer A549 cells. Anticancer Drugs, 2013, 24(5):494-503.
25. 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.
26. Gong Z, Liu W, You N, et al. Prognostic significance of metadherin overexpression in hepatitis B virus-related hepatocellular carcinoma.Oncol Rep, 2012, 27(6):2073-2079.
27. Lee CW, Kuo WL, Yu MC, et al. The expression of cytokeratin 19 in lymph nodes was a poor prognostic factor for hepatocellular carcinoma after hepatic resection. World J Surg Oncol, 2013, 11(1):136.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Expression of Metaherin and Its Clinical Significance for Hepatitis B Related Hepatocellular Carcinoma

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