Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
January 2013 Volume 5 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
January 2013 Volume 5 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Epithelial-mesenchymal transition expression profiles as a prognostic factor for disease-free survival in hepatocellular carcinoma: Clinical significance of transforming growth factor-β signaling

  • Authors:
    • Kosuke Mima
    • Hiromitsu Hayashi
    • Hideyuki Kuroki
    • Shigeki Nakagawa
    • Hirohisa  Okabe
    • Akira Chikamoto
    • Masayuki Watanabe
    • Toru Beppu
    • Hideo Baba
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan
  • Pages: 149-154
    |
    Published online on: October 5, 2012
       https://doi.org/10.3892/ol.2012.954
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Epithelial­‑mesenchymal transition (EMT) plays a pivotal role in cancer invasion and metastasis, and transforming growth factor (TGF)‑β signaling is a potent inducer of EMT. However, the clinical significance of the correlation between EMT marker expression and TGF‑β signaling in hepatocellular carcinoma (HCC) patients remains unknown. In this study, immunohistochemistry was used to analyze the expression of EMT markers and phospho‑Smad2 nuclear positivity, and their association with clinicopathological features in 150 HCC patients. E‑cadherinhigh/vimentinlow and E‑cadherinlow/vimentinhigh expression profiles were determined in 55 (36.7%) and 21 (14.0%) patients, respectively. The E‑cadherinlow/vimentinhigh expression profile was significantly correlated with poor tumor differentiation (P<0.001), vascular invasion (P=0.007) and extrahepatic recurrence following curative surgery (P=0.026). Furthermore, the E‑cadherinlow/vimentinhigh expression profile was significantly correlated with shorter disease-free survival compared to E‑cadherinhigh/vimentinlow (P=0.002). Forty-one patients (27.3%) were demonstrated to have high phospho‑Smad2 nuclear positivity, which was significantly correlated with the E‑cadherinlow/vimentinhigh expression profile (P<0.001). In conclusion, this study suggests that EMT expression profiles are useful prognostic markers for disease-free survival in HCC patients, and that the E‑cadherinlow/vimentinhigh expression profile is closely associated with high-grade malignant behavior such as tumoral vascular invasion and metastasis in HCC. Additionally, TGF‑β‑mediated EMT may play an important role in the aggressiveness of HCC.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

El-Serag HB: Hepatocellular carcinoma. N Engl J Med. 365:1118–1127. 2011. View Article : Google Scholar : PubMed/NCBI

2 

Thiery JP, Acloque H, Huang RY and Nieto MA: Epithelialmesenchymal transitions in development and disease. Cell. 139:871–890. 2009. View Article : Google Scholar : PubMed/NCBI

3 

Moody SE, Perez D, Pan TC, et al: The transcriptional repressor Snail promotes mammary tumor recurrence. Cancer Cell. 8:197–209. 2005. View Article : Google Scholar : PubMed/NCBI

4 

Shioiri M, Shida T, Koda K, et al: Slug expression is an independent prognostic parameter for poor survival in colorectal carcinoma patients. Br J Cancer. 94:1816–1822. 2006. View Article : Google Scholar : PubMed/NCBI

5 

Yang MH, Chen CL, Chau GY, et al: Comprehensive analysis of the independent effect of twist and snail in promoting metastasis of hepatocellular carcinoma. Hepatology. 50:1464–1474. 2009. View Article : Google Scholar : PubMed/NCBI

6 

Zhou YM, Cao L, Li B, et al: Clinicopathological significance of ZEB1 protein in patients with hepatocellular carcinoma. Ann Surg Oncol. 19:1700–1706. 2011. View Article : Google Scholar : PubMed/NCBI

7 

Siegel PM and Massagué J: Cytostatic and apoptotic actions of TGF-beta in homeostasis and cancer. Nat Rev Cancer. 3:807–821. 2003. View Article : Google Scholar : PubMed/NCBI

8 

Mima K, Okabe H, Ishimoto T, et al: CD44s regulates the TGF-β-mediated mesenchymal phenotype and is associated with poor prognosis in patients with hepatocellular carcinoma. Cancer Res. 72:3414–3423. 2012.PubMed/NCBI

9 

Liver Cancer Study Group of Japan: The General Rules for the Clinical and Pathological Study of Primary Liver Cancer. Kanehara, Tokyo: 2009

10 

Minagawa M, Ikai I, Matsuyama Y, Yamaoka Y and Makuuchi M: Staging of hepatocellular carcinoma: assessment of the Japanese TNM and AJCC/UICC TNM systems in a cohort of 13,772 patients in Japan. Ann Surg. 245:909–922. 2007. View Article : Google Scholar : PubMed/NCBI

11 

Vauthey JN, Lauwers GY, Esnaola NF, et al: Simplified staging for hepatocellular carcinoma. J Clin Oncol. 20:1527–1536. 2002. View Article : Google Scholar : PubMed/NCBI

12 

Okabe H, Beppu T, Hayashi H, et al: Hepatic stellate cells accelerate the malignant behavior of cholangiocarcinoma cells. Ann Surg Oncol. 18:1175–1184. 2011. View Article : Google Scholar : PubMed/NCBI

13 

Yang MH, Hsu DS, Wang HW, et al: Bmi1 is essential in Twist1-induced epithelial-mesenchymal transition. Nat Cell Biol. 12:982–992. 2010. View Article : Google Scholar : PubMed/NCBI

14 

Iwatsuki M, Mimori K, Fukagawa T, et al: The clinical significance of vimentin-expressing gastric cancer cells in bone marrow. Ann Surg Oncol. 17:2526–2533. 2010. View Article : Google Scholar : PubMed/NCBI

15 

Vora HH, Patel NA, Rajvik KN, et al: Cytokeratin and vimentin expression in breast cancer. Int J Biol Markers. 24:38–46. 2009.PubMed/NCBI

16 

Padua D, Zhang XH, Wang Q, et al: TGFbeta primes breast tumors for lung metastasis seeding through angiopoietin-like 4. Cell. 133:66–77. 2008. View Article : Google Scholar : PubMed/NCBI

17 

Yin JJ, Selander K, Chirgwin JM, et al: TGF-beta signaling blockade inhibits PTHrP secretion by breast cancer cells and bone metastases development. J Clin Invest. 103:197–206. 1999. View Article : Google Scholar : PubMed/NCBI

18 

Bedossa P, Peltier E, Terris B, Franco D and Poynard T: Transforming growth factor-beta 1 (TGF-beta 1) and TGF-beta 1 receptors in normal, cirrhotic, and neoplastic human livers. Hepatology. 21:760–766. 1995.PubMed/NCBI

19 

Abou-Shady M, Baer HU, Friess H, et al: Transforming growth factor betas and their signaling receptors in human hepatocellular carcinoma. Am J Surg. 177:209–215. 1999. View Article : Google Scholar : PubMed/NCBI

20 

Lee TK, Man K, Poon RT, et al: Signal transducers and activators of transcription 5b activation enhances hepatocellular carcinoma aggressiveness through induction of epithelial-mesenchymal transition. Cancer Res. 66:9948–9956. 2006. View Article : Google Scholar

21 

Chen L, Chan TH, Yuan YF, et al: CHD1L promotes hepatocellular carcinoma progression and metastasis in mice and is associated with these processes in human patients. J Clin Invest. 120:1178–1191. 2010. View Article : Google Scholar : PubMed/NCBI

22 

Chung KY, Cheng IK, Ching AK, Chu JH, Lai PB and Wong N: Block of proliferation 1 (BOP1) plays an oncogenic role in hepatocellular carcinoma by promoting epithelial-to-mesenchymal transition. Hepatology. 54:307–318. 2011. View Article : Google Scholar : PubMed/NCBI

23 

Fu J, Chen Y, Cao J, et al: p28GANK overexpression accelerates hepatocellular carcinoma invasiveness and metastasis via phosphoinositol 3-kinase/AKT/hypoxia-inducible factor-1alpha pathways. Hepatology. 53:181–192. 2011. View Article : Google Scholar

24 

Kim H, Choi GH, Na DC, et al: Human hepatocellular carcinomas with “stemness”-related marker expression: keratin 19 expression and a poor prognosis. Hepatology. 54:1707–1717. 2011.

25 

Wang J, Chen L, Li Y and Guan XY: Overexpression of cathepsin Z contributes to tumor metastasis by inducing epithelial-mesenchymal transition in hepatocellular carcinoma. PLoS One. 6:e249672011. View Article : Google Scholar : PubMed/NCBI

26 

Yokomizo C, Yamaguchi K, Itoh Y, et al: High expression of p300 in HCC predicts shortened overall survival in association with enhanced epithelial mesenchymal transition of HCC cells. Cancer Lett. 310:140–147. 2011. View Article : Google Scholar : PubMed/NCBI

27 

Zhu K, Dai Z, Pan Q, et al: Metadherin promotes hepatocellular carcinoma metastasis through induction of epithelial-mesenchymal transition. Clin Cancer Res. 17:7294–7302. 2011. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Mima K, Hayashi H, Kuroki H, Nakagawa S, Okabe H, Chikamoto A, Watanabe M, Beppu T and Baba H: Epithelial-mesenchymal transition expression profiles as a prognostic factor for disease-free survival in hepatocellular carcinoma: Clinical significance of transforming growth factor-β signaling. Oncol Lett 5: 149-154, 2013.
APA
Mima, K., Hayashi, H., Kuroki, H., Nakagawa, S., Okabe, H., Chikamoto, A. ... Baba, H. (2013). Epithelial-mesenchymal transition expression profiles as a prognostic factor for disease-free survival in hepatocellular carcinoma: Clinical significance of transforming growth factor-β signaling. Oncology Letters, 5, 149-154. https://doi.org/10.3892/ol.2012.954
MLA
Mima, K., Hayashi, H., Kuroki, H., Nakagawa, S., Okabe, H., Chikamoto, A., Watanabe, M., Beppu, T., Baba, H."Epithelial-mesenchymal transition expression profiles as a prognostic factor for disease-free survival in hepatocellular carcinoma: Clinical significance of transforming growth factor-β signaling". Oncology Letters 5.1 (2013): 149-154.
Chicago
Mima, K., Hayashi, H., Kuroki, H., Nakagawa, S., Okabe, H., Chikamoto, A., Watanabe, M., Beppu, T., Baba, H."Epithelial-mesenchymal transition expression profiles as a prognostic factor for disease-free survival in hepatocellular carcinoma: Clinical significance of transforming growth factor-β signaling". Oncology Letters 5, no. 1 (2013): 149-154. https://doi.org/10.3892/ol.2012.954
Copy and paste a formatted citation
x
Spandidos Publications style
Mima K, Hayashi H, Kuroki H, Nakagawa S, Okabe H, Chikamoto A, Watanabe M, Beppu T and Baba H: Epithelial-mesenchymal transition expression profiles as a prognostic factor for disease-free survival in hepatocellular carcinoma: Clinical significance of transforming growth factor-β signaling. Oncol Lett 5: 149-154, 2013.
APA
Mima, K., Hayashi, H., Kuroki, H., Nakagawa, S., Okabe, H., Chikamoto, A. ... Baba, H. (2013). Epithelial-mesenchymal transition expression profiles as a prognostic factor for disease-free survival in hepatocellular carcinoma: Clinical significance of transforming growth factor-β signaling. Oncology Letters, 5, 149-154. https://doi.org/10.3892/ol.2012.954
MLA
Mima, K., Hayashi, H., Kuroki, H., Nakagawa, S., Okabe, H., Chikamoto, A., Watanabe, M., Beppu, T., Baba, H."Epithelial-mesenchymal transition expression profiles as a prognostic factor for disease-free survival in hepatocellular carcinoma: Clinical significance of transforming growth factor-β signaling". Oncology Letters 5.1 (2013): 149-154.
Chicago
Mima, K., Hayashi, H., Kuroki, H., Nakagawa, S., Okabe, H., Chikamoto, A., Watanabe, M., Beppu, T., Baba, H."Epithelial-mesenchymal transition expression profiles as a prognostic factor for disease-free survival in hepatocellular carcinoma: Clinical significance of transforming growth factor-β signaling". Oncology Letters 5, no. 1 (2013): 149-154. https://doi.org/10.3892/ol.2012.954
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team