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
March-2018 Volume 15 Issue 3

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
March-2018 Volume 15 Issue 3

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 Open Access

CD133 expression and α‑fetoprotein levels define novel prognostic subtypes of HBV‑associated hepatocellular carcinoma: A long‑term follow‑up analysis

  • Authors:
    • Xiao‑Meng Dai
    • Sheng‑Li Yang
    • Xiu‑Mei Zheng
    • George G. Chen
    • Jing Chen
    • Tao Zhang
  • View Affiliations / Copyright

    Affiliations: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China, Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong, SAR, P.R. China
    Copyright: © Dai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2985-2991
    |
    Published online on: December 28, 2017
       https://doi.org/10.3892/ol.2017.7704
  • 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

Hepatocellular carcinoma (HCC) is a highly heterogeneous type of tumor, which may be caused by the stem/progenitor cell features of particular HCC cells. Recent studies have subclassified HCC into different prognostic subtypes according to just one stemness‑associated marker. However, one stemness‑associated marker is not sufficient to clearly define cancer stem cells, or to decipher the heterogeneous nature of HCC. For a more precise subtype classification for prognostic application, a combination of multiple stemness‑associated markers is required. Cluster of differentiation 133 (CD133) and α‑fetoprotein (AFP) are common stemness‑associated markers for HCC that have not yet been employed for HCC subtype classification. In the present study, CD133 expression was assessed by immunohistochemistry in 127 hepatitis B virus‑associated HCC tumor specimens. Based on CD133 immunostaining and serum AFP levels, the HCC cases were subclassified into four subtypes, which demonstrated different clinicopathological features and varying prognoses. Among the four subtypes, the number of tumor lesions, histological grade and vascular invasion were significantly different (P=0.002, P=0.018 and P=0.022, respectively). CD133+AFP+ HCC was associated with a rela­tively poor prognosis, CD133-AFP‑ HCC was associated with a relatively good prognosis, while CD133+AFP‑ HCC and CD133‑AFP+ HCC were associated with an intermediate prognosis. These prognostic values were confirmed by borderline or statistical significance (between all groups, overall survival, P=0.061; recurrence‑free survival, P=0.015). These results define a novel and simple system, based on CD133 and AFP, for classifying HCC into four distinct prognostic subtypes. This classification system may aid the assessment of patients with HCC for personalized therapy.
View Figures

Figure 1

Figure 2

View References

1 

Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D and Bray F: Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 136:E359–E386. 2015. View Article : Google Scholar : PubMed/NCBI

2 

Altekruse SF, McGlynn KA, Dickie LA and Kleiner DE: Hepatocellular carcinoma confirmation, treatment, and survival in surveillance, epidemiology, and end results registries, 1992–2008. Hepatology. 55:476–482. 2012. View Article : Google Scholar : PubMed/NCBI

3 

Bosch FX, Ribes J, Cléries R and Diaz M: Epidemiology of hepatocellular carcinoma. Clin Liver Dis. 9:191–211. 2005. View Article : Google Scholar : PubMed/NCBI

4 

Tanaka S and Arii S: Molecularly targeted therapy for hepatocellular carcinoma. Cancer Sci. 100:1–8. 2009. View Article : Google Scholar : PubMed/NCBI

5 

Lau WY and Lai EC: The current role of radiofrequency ablation in the management of hepatocellular carcinoma: A systematic review. Ann Surg. 249:20–25. 2009. View Article : Google Scholar : PubMed/NCBI

6 

Thorgeirsson SS and Grisham JW: Molecular pathogenesis of human hepatocellular carcinoma. Nat Genet. 31:339–346. 2002. View Article : Google Scholar : PubMed/NCBI

7 

Yamashita T, Forgues M, Wang W, Kim JW, Ye Q, Jia H, Budhu A, Zanetti KA, Chen Y, Qin LX, et al: EpCAM and alpha-fetoprotein expression defines novel prognostic subtypes of hepatocellular carcinoma. Cancer Res. 68:1451–1461. 2008. View Article : Google Scholar : PubMed/NCBI

8 

Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C and De Maria R: Identification and expansion of human colon-cancer-initiating cells. Nature. 445:111–115. 2007. View Article : Google Scholar : PubMed/NCBI

9 

Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ and Clarke MF: Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA. 100:pp. 3983–3988. 2003; View Article : Google Scholar : PubMed/NCBI

10 

Bonnet D and Dick JE: Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med. 3:730–737. 1997. View Article : Google Scholar : PubMed/NCBI

11 

Kim H, Choi GH, Na DC, Ahn EY, Kim GI, Lee JE, Cho JY, Yoo JE, Choi JS and Park YN: Human hepatocellular carcinomas with ‘Stemness’-related marker expression: Keratin 19 expression and a poor prognosis. Hepatology. 54:1707–1717. 2011. View Article : Google Scholar : PubMed/NCBI

12 

Terris B, Cavard C and Perret C: EpCAM, a new marker for cancer stem cells in hepatocellular carcinoma. J Hepatol. 52:280–281. 2010. View Article : Google Scholar : PubMed/NCBI

13 

Yang SL, Liu LP, Yang S, Liu L, Ren JW, Fang X, Chen GG and Lai PB: Preoperative serum α-fetoprotein and prognosis after hepatectomy for hepatocellular carcinoma. Br J Surg. 103:716–724. 2016. View Article : Google Scholar : PubMed/NCBI

14 

Reya T and Clevers H: Wnt signalling in stem cells and cancer. Nature. 434:843–850. 2005. View Article : Google Scholar : PubMed/NCBI

15 

Ma S, Tang KH, Chan YP, Lee TK, Kwan PS, Castilho A, Ng I, Man K, Wong N, To KF, et al: miR-130b promotes CD133(+) liver tumor-initiating cell growth and self-renewal via tumor protein 53-induced nuclear protein 1. Cell Stem Cell. 7:694–707. 2010. View Article : Google Scholar : PubMed/NCBI

16 

Altman DG, McShane LM, Sauerbrei W and Taube SE: Reporting recommendations for tumor marker prognostic studies (REMARK): Explanation and elaboration. PLoS Med. 9:e10012162012. View Article : Google Scholar : PubMed/NCBI

17 

Moons KG, Altman DG, Reitsma JB and Collins GS: Transparent Reporting of a Multivariate PredictionModel for Individual Prognosis or Development Initiative: New guideline for the reporting of studies developing, validating, or updating a multivariable clinical prediction model: The TRIPOD statement. Adv Anat Pathol. 22:303–305. 2015. View Article : Google Scholar : PubMed/NCBI

18 

Chan SL, Mo F, Johnson PJ, Siu DY, Chan MH, Lau WY, Lai PB, Lam CW, Yeo W and Yu SC: Performance of serum α-fetoprotein levels in the diagnosis of hepatocellular carcinoma in patients with a hepatic mass. HPB (Oxford). 16:366–372. 2014. View Article : Google Scholar : PubMed/NCBI

19 

Kang YK, Hong SW, Lee H and Kim WH: Prognostic implications of ezrin expression in human hepatocellular carcinoma. Mol Carcinog. 49:798–804. 2010.PubMed/NCBI

20 

Lee JS, Chu IS, Heo J, Calvisi DF, Sun Z, Roskams T, Durnez A, Demetris AJ and Thorgeirsson SS: Classification and prediction of survival in hepatocellular carcinoma by gene expression profiling. Hepatology. 40:667–676. 2004. View Article : Google Scholar : PubMed/NCBI

21 

Yamashita T, Ji J, Budhu A, Forgues M, Yang W, Wang HY, Jia H, Ye Q, Qin LX, Wauthier E, et al: EpCAM-positive hepatocellular carcinoma cells are tumor-initiating cells with stem/progenitor cell features. Gastroenterology. 136:1012–1024. 2009. View Article : Google Scholar : PubMed/NCBI

22 

Schmelzer E, Wauthier E and Reid LM: The phenotypes of pluripotent human hepatic progenitors. Stem Cells. 24:1852–1858. 2006. View Article : Google Scholar : PubMed/NCBI

23 

Roskams T: Liver stem cells and their implication in hepatocellular and cholangiocarcinoma. Oncogene. 25:3818–3822. 2006. View Article : Google Scholar : PubMed/NCBI

24 

Ishii T, Yasuchika K, Suemori H, Nakatsuji N, Ikai I and Uemoto S: Alpha-fetoprotein producing cells act as cancer progenitor cells in human cholangiocarcinoma. Cancer Lett. 294:25–34. 2010. View Article : Google Scholar : PubMed/NCBI

25 

Ma S, Chan KW, Hu L, Lee TK, Wo JY, Ng IO, Zheng BJ and Guan XY: Identification and characterization of tumorigenic liver cancer stem/progenitor cells. Gastroenterology. 132:2542–2556. 2007. View Article : Google Scholar : PubMed/NCBI

26 

Lindgren D, Boström AK, Nilsson K, Hansson J, Sjölund J, Möller C, Jirström K, Nilsson E, Landberg G, Axelson H and Johansson ME: Isolation and characterization of Progenitor-like cells from human renal proximal tubules. Am J Pathol. 178:828–837. 2011. View Article : Google Scholar : PubMed/NCBI

27 

Schmelzer E, Zhang L, Bruce A, Wauthier E, Ludlow J, Yao HL, Moss N, Melhem A, McClelland R, Turner W, et al: Human hepatic stem cells from fetal and postnatal donors. J Exp Med. 204:1973–1987. 2007. View Article : Google Scholar : PubMed/NCBI

28 

Richardson GD, Robson CN, Lang SH, Neal DE, Maitland NJ and Collins AT: CD133, a novel marker for human prostatic epithelial stem cells. J Cell Sci. 117:3539–3545. 2004. View Article : Google Scholar : PubMed/NCBI

29 

Uchida N, Buck DW, He DP, Reitsma MJ, Masek M, Phan TV, Tsukamoto AS, Gage FH and Weissman IL: Direct isolation of human central nervous system stem cells. Proc Natl Acad Sci USA. 97:pp. 14720–14725. 2000; View Article : Google Scholar : PubMed/NCBI

30 

Yin AH, Miraglia S, Zanjani ED, Almeida-Porada G, Ogawa M, Leary AG, Olweus J, Kearney J and Buck DW: AC133, a novel marker for human hematopoietic stem and progenitor cells. Blood. 90:5002–5012. 1997.PubMed/NCBI

31 

Yin S, Li J, Hu C, Chen X, Yao M, Yan M, Jiang G, Ge C, Xie H, Wan D, et al: CD133 positive hepatocellular carcinoma cells possess high capacity for tumorigenicity. Int J Cancer. 120:1444–1450. 2007. View Article : Google Scholar : PubMed/NCBI

32 

Parpart S, Roessler S, Dong F, Rao V, Takai A, Ji J, Qin LX, Ye QH, Jia HL, Tang ZY and Wang XW: Modulation of miR-29 expression by α-fetoprotein is linked to the hepatocellular carcinoma epigenome. Hepatology. 60:872–883. 2014. View Article : Google Scholar : PubMed/NCBI

33 

Sasaki A, Kamiyama T, Yokoo H, Nakanishi K, Kubota K, Haga H, Matsushita M, Ozaki M, Matsuno Y and Todo S: Cytoplasmic expression of CD133 is an important risk factor for overall survival in hepatocellular carcinoma. Oncol Rep. 24:537–546. 2010. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Dai XM, Yang SL, Zheng XM, Chen GG, Chen J and Zhang T: CD133 expression and α‑fetoprotein levels define novel prognostic subtypes of HBV‑associated hepatocellular carcinoma: A long‑term follow‑up analysis. Oncol Lett 15: 2985-2991, 2018.
APA
Dai, X., Yang, S., Zheng, X., Chen, G.G., Chen, J., & Zhang, T. (2018). CD133 expression and α‑fetoprotein levels define novel prognostic subtypes of HBV‑associated hepatocellular carcinoma: A long‑term follow‑up analysis. Oncology Letters, 15, 2985-2991. https://doi.org/10.3892/ol.2017.7704
MLA
Dai, X., Yang, S., Zheng, X., Chen, G. G., Chen, J., Zhang, T."CD133 expression and α‑fetoprotein levels define novel prognostic subtypes of HBV‑associated hepatocellular carcinoma: A long‑term follow‑up analysis". Oncology Letters 15.3 (2018): 2985-2991.
Chicago
Dai, X., Yang, S., Zheng, X., Chen, G. G., Chen, J., Zhang, T."CD133 expression and α‑fetoprotein levels define novel prognostic subtypes of HBV‑associated hepatocellular carcinoma: A long‑term follow‑up analysis". Oncology Letters 15, no. 3 (2018): 2985-2991. https://doi.org/10.3892/ol.2017.7704
Copy and paste a formatted citation
x
Spandidos Publications style
Dai XM, Yang SL, Zheng XM, Chen GG, Chen J and Zhang T: CD133 expression and α‑fetoprotein levels define novel prognostic subtypes of HBV‑associated hepatocellular carcinoma: A long‑term follow‑up analysis. Oncol Lett 15: 2985-2991, 2018.
APA
Dai, X., Yang, S., Zheng, X., Chen, G.G., Chen, J., & Zhang, T. (2018). CD133 expression and α‑fetoprotein levels define novel prognostic subtypes of HBV‑associated hepatocellular carcinoma: A long‑term follow‑up analysis. Oncology Letters, 15, 2985-2991. https://doi.org/10.3892/ol.2017.7704
MLA
Dai, X., Yang, S., Zheng, X., Chen, G. G., Chen, J., Zhang, T."CD133 expression and α‑fetoprotein levels define novel prognostic subtypes of HBV‑associated hepatocellular carcinoma: A long‑term follow‑up analysis". Oncology Letters 15.3 (2018): 2985-2991.
Chicago
Dai, X., Yang, S., Zheng, X., Chen, G. G., Chen, J., Zhang, T."CD133 expression and α‑fetoprotein levels define novel prognostic subtypes of HBV‑associated hepatocellular carcinoma: A long‑term follow‑up analysis". Oncology Letters 15, no. 3 (2018): 2985-2991. https://doi.org/10.3892/ol.2017.7704
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