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Astrocyte elevated gene-1 is a novel biomarker of epithelial–mesenchymal transition and progression of hepatocellular carcinoma in two China regions

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Tumor Biology

Abstract

Astrocyte elevated gene-1 (AEG-1) is involved in important biological processes including cell invasion, metastasis, and carcinogenesis. However, its clinical significance has remained largely unknown in hepatocellular carcinoma. Here, specimens from 144 patients with hepatocellular carcinomas in Beijing and Heilongjiang regions were investigated by immunohistochemical staining for AEG-1, vimentin, and E-cadherin expressions. A clinicopathological study revealed that AEG-1 expression level in tumor cells was significantly correlated with TNM stage (P = 0.001) and Edmonson grade (P < 0.0001). In addition, AEG-1, vimentin, and E-cadherin (epithelial–mesenchymal transition (EMT) biomarker) expressions were correlated with each other. These findings suggest that AEG-1 may be an epithelial–mesenchymal transition-associated biomarker in human hepatocellular carcinoma and play important roles in the progression of hepatocellular carcinoma. In addition, the AEG-1 gene is a potential target for elimination of hepatocellular carcinoma in the future.

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References

  1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62:10–29.

    Article  PubMed  Google Scholar 

  2. Mittal S, El-Serag HB. Epidemiology of hepatocellular carcinoma: consider the population. J Clin Gastroenterol. 2013;47(Suppl):S2–6.

    Article  PubMed  Google Scholar 

  3. Padhya KT, Marrero JA, Singal AG. Recent advances in the treatment of hepatocellular carcinoma. Curr Opin Gastroenterol. 2013;29:285–92.

    Article  PubMed  CAS  Google Scholar 

  4. van Zijl F, Zulehner G, Petz M, Schneller D, Kornauth C, Hau M, et al. Epithelial–mesenchymal transition in hepatocellular carcinoma. Future Oncol. 2009;5:1169–79.

    Article  PubMed  Google Scholar 

  5. Lee TK, Poon RT, Yuen AP, et al. Twist overexpression correlates with hepatocellular carcinoma metastasis through induction of epithelial–mesenchymal transition. Clin Cancer Res. 2006;12:5369–76.

    Article  PubMed  CAS  Google Scholar 

  6. Su ZZ, Kang DC, Chen Y, et al. Identification and cloning of human astrocyte genes displaying elevated expression after infection with HIV-1 or exposure to HIV-1 envelope glycoprotein by rapid subtraction hybridization, RasH. Oncogene. 2002;21:3592–602.

    Article  PubMed  CAS  Google Scholar 

  7. Kang DC, Su ZZ, Sarkar D, et al. Cloning and characterization of HIV-1-inducible astrocyte elevated gene-1, AEG-1. Gene. 2005;353:8–15.

    Article  PubMed  CAS  Google Scholar 

  8. Brown DM, Ruoslahti E. Metadherin, a cell surface protein in breast tumors that mediates lung metastasis. Cancer Cell. 2004;5:365–74.

    Article  PubMed  CAS  Google Scholar 

  9. Meng X, Zhu D, Yang S, et al. Cytoplasmic metadherin (MTDH) provides survival advantage under conditions of stress by acting as RNA-binding protein. J Biol Chem. 2012;287:4485–91.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  10. Thirkettle HJ, Mills IG, Whitaker HC, et al. Nuclear LYRIC/AEG-1 interacts with PLZF and relieves PLZF-mediated repression. Oncogene. 2009;28:3663–70.

    Article  PubMed  CAS  Google Scholar 

  11. Yoo BK, Emdad L, Sarkar D, et al. Astrocyte elevated gene-1 (AEG-1): a multifunctional regulator of normal and abnormal physiology. Pharmacol Ther. 2011;130:1–8.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  12. Emdad L, Lee SG, Fisher PB, et al. Astrocyte elevated gene-1 (AEG-1) functions as an oncogene and regulates angiogenesis. Proc Natl Acad Sci U S A. 2009;106:21300–5.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  13. Lee HJ, Jung DB, Kim SH, et al. Inhibition of hypoxia inducible factor alpha and astrocyte-elevated gene-1 mediates cryptotanshinone exerted antitumor activity in hypoxic PC-3 cells. Evid Based Complement Alternat Med. 2012;2012:1–13.

    Google Scholar 

  14. Noch E, Bookland M, Khalili K. Astrocyte-elevated gene-1 (AEG-1) induction by hypoxia and glucose deprivation in glioblastoma. Cancer Biol Ther. 2011;11:32–9.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  15. Li C, Song H, Geng J, et al. Significance of AEG-1 expression in correlation with VEGF, microvessel density and clinicopathological characteristics in triple-negative breast cancer. J Surg Oncol. 2011;103:184–92.

    Article  PubMed  CAS  Google Scholar 

  16. Li C, Song H, Geng J, et al. AEG-1 overexpression: a novel indicator for peritoneal dissemination and lymph node metastasis in epithelial ovarian cancers. Int J Gynecol Cancer. 2011;21:602–8.

    Article  PubMed  Google Scholar 

  17. Li C, Song H, Geng J, et al. Elevated expression of AEG-1 is correlated with cisplatin-based chemoresistance and shortened outcome in patients with stages III–IV serous ovarian carcinoma. Histopathology. 2012;60:953–63.

    Article  PubMed  Google Scholar 

  18. Song H, Li C, Geng J, et al. Prognostic significance of expression in colorectal carcinoma. Int J Colorectal Dis. 2010;25:1201–9.

    Article  PubMed  Google Scholar 

  19. Erdem H, Yildirim U, Uzunlar AK, et al. Relationship among expression of basic-fibroblast growth factor, MTDH/astrocyte elevated gene-1, adenomatous polyposis coli, matrix metalloproteinase 9, and COX-2 markers with prognostic factors in prostate carcinomas. Niger J Clin Pract. 2013;16:418–23.

    Article  PubMed  CAS  Google Scholar 

  20. 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;58:2873–80.

    Article  PubMed  CAS  Google Scholar 

  21. Noch EK, Khalili K. The role of AEG-1/MTDH/LYRIC in the pathogenesis of central nervous system disease. Adv Cancer Res. 2013;120:159–92.

    Article  PubMed  CAS  Google Scholar 

  22. Srivastava J, Siddiq A, Emdad L, et al. Astrocyte elevated gene-1 promotes hepatocarcinogenesis: novel insights from a mouse model. Hepatology. 2012;56:1782–91.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  23. Wan L, Kang Y. Pleiotropic roles of AEG-1/MTDH/LYRIC in breast cancer. Adv Cancer Res. 2013;120:113–34.

    Article  PubMed  CAS  Google Scholar 

  24. Emdad L, Das SK, Dasgupta S, et al. AEG-1/MTDH/LYRIC: signaling pathways, downstream genes, interacting proteins, and regulation of tumor angiogenesis. Adv Cancer Res. 2013;120:75–111.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  25. Sarkar D. AEG-1/MTDH/LYRIC in liver cancer. Adv Cancer Res. 2013;120:193–221.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  26. 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.

    Article  PubMed  CAS  Google Scholar 

  27. He XX, Chang Y, Meng FY, et al. MicroRNA-375 targets AEG-1 in hepatocellular carcinoma and suppresses liver cancer cell growth in vitro and in vivo. Oncogene. 2012;31:3357–69.

    Article  PubMed  CAS  Google Scholar 

  28. Zhu K, Dai Z, Pan Q, et al. Metadherin promotes hepatocellular carcinoma metastasis through induction of epithelial–mesenchymal transition. Clin Cancer Res. 2011;17:7294–302.

    Article  PubMed  CAS  Google Scholar 

  29. 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;102:1151–7.

    Article  PubMed  CAS  Google Scholar 

  30. Wei J, Li Z, Chen W, et al. AEG-1 participates in TGF-beta1-induced EMT through p38 MAPK activation. Cell Biol Int. 2013;37:1016–21.

    Article  PubMed  CAS  Google Scholar 

  31. Kohles N, Nagel D, Jüngst D, Stieber P, Holdenrieder S. Predictive value of immunogenic cell death biomarkers HMGB1, sRAGE, and DNase in liver cancer patients receiving transarterial chemoembolization therapy. Tumour Biol. 2012;33:2401–9.

    Article  PubMed  CAS  Google Scholar 

  32. Yao N, Yao D, Wang L, et al. Inhibition of autocrine IGF-II on effect of human HepG2 cell proliferation and angiogenesis factor expression. Tumor Biol. 2012;33:1767–76.

    Article  CAS  Google Scholar 

  33. Sun Y, Sun T, Li C, et al. A polysaccharide from the fungi of Huaier exhibits anti-tumor potential and immunomodulatory effects. Carbohydr Polym. 2013;92:577–82.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This paper was supported by the Twelve-fifth Key Science and Technology Five Year Plan of China (no. 2012BAI15B08).

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Authors and Affiliations

  1. Intervention Therapy Center of Liver Diseases, Beijing You’an Hospital, Capital Medical University, Beijing, 100069, China

    Jiasheng Zheng, Cong Li, Meijun Hao, Shoupeng Sheng, Yu Sun, Honghai Zhang, Jiang Long & Caixia Hu

  2. Beijing Institute of Liver Diseases, Beijing You’an Hospital, Capital Medical University, Beijing, 100069, China

    Jiasheng Zheng, Cong Li, Meijun Hao, Shoupeng Sheng, Yu Sun, Honghai Zhang, Jiang Long & Caixia Hu

  3. Department of Infectious Disease, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China

    Xia Wu & Yingzhuo Yang

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  1. Jiasheng Zheng
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  2. Cong Li
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  10. Caixia Hu
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Correspondence to Jiasheng Zheng.

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Zheng, J., Li, C., Wu, X. et al. Astrocyte elevated gene-1 is a novel biomarker of epithelial–mesenchymal transition and progression of hepatocellular carcinoma in two China regions. Tumor Biol. 35, 2265–2269 (2014). https://doi.org/10.1007/s13277-013-1300-3

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  • DOI: https://doi.org/10.1007/s13277-013-1300-3

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