Skip to main content

Advertisement

Log in

Role of CD44 expression in non-tumor tissue on intrahepatic recurrence of hepatocellular carcinoma

  • Original Article
  • Published:
International Journal of Clinical Oncology Aims and scope Submit manuscript

Abstract

Background

CD44 is well known to be one of the cancer stem cell markers and is a cell-surface glycoprotein involved in cell–cell interactions, cell adhesion, and cell migration. We investigated the role of CD44 expression in both tumor and non-tumor tissues on recurrence of hepatocellular carcinoma (HCC).

Methods

Forty-eight patients with HCC who underwent hepatic resection at our institution were enrolled in this study. CD44 expressions in both tumor and non-tumor tissues were examined using real time reverse transcription-polymerase chain reaction. The patients were divided into two groups: high and low gene-expression group, based on the CD44 expression level. We compared the clinicopathological factors between the high expression and low expression groups in both tumor and non-tumor tissues.

Results

In the tumor tissues, the gene-expression levels of CD44 did not correlate with any clinicopathological parameters. The disease-free survival rate showed no significant difference between the two groups. In non-tumor tissues, although there was no significant relationship between the CD44 expression levels and clinicopathological factors, disease-free survival rate in the CD44 low expression group was significantly better than that in the CD44 high expression group (P < 0.05). In multivariate analysis, the risk factors in tumor recurrence were presence of microscopic portal invasion and high expression level of CD44.

Conclusion

The CD44 expressions in the non-tumor tissues may predict HCC recurrence.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

HCC:

Hepatocellular carcinoma

RT-PCR:

Reverse transcription-polymerase chain reaction

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

AST:

Aspartate aminotransferase

ALT:

Alanine transaminase

WBC:

White blood cell

PT:

Prothrombin time

ICGR15 :

Indocyanine green retention rate at 15 min

AFP:

Alpha-fetoprotein

DCP:

Des-gamma-carboxy prothrombin

References

  1. Llovet JM, Beaugrand M (2003) Hepatocellular carcinoma: present status and future prospects. J Hepatol 38:S136–S149

    Article  PubMed  Google Scholar 

  2. Bruix J, Boix L, Sala M et al (2004) Focus on hepatocellular carcinoma. Cancer Cell 5:215–219

    Article  PubMed  CAS  Google Scholar 

  3. Lee JG, Kang CM, Park JS et al (2006) The actual five-year survival rate of hepatocellular carcinoma patients after curative resection. Yonsei Med J 47:105–112

    Article  PubMed  Google Scholar 

  4. Bendall LJ, Nillson SK, Khan NI et al (2004) Role of CD44 variant exon 6 in acute lymphoblastic leukemia: association with altered bone marrow localization and increased tumour burden. Leukemia 18:1308–1311

    Article  PubMed  CAS  Google Scholar 

  5. Ponta H, Sherman L, Herrlich PA (2003) CD44: from adhesion molecules to signaling regulators. Nat Rev Mol Cell Biol 4:33–45

    Article  PubMed  CAS  Google Scholar 

  6. Cooper DL, Dougherty GJ (1995) To metastasize or not? Selection of CD44 splice sites. Nat Med 1:635–637

    Article  PubMed  CAS  Google Scholar 

  7. Liu J, Jiang G (2006) CD44 and hematologic malignancies. Cell Mol Immunol 3:359–365

    PubMed  CAS  Google Scholar 

  8. Naor D, Nedvetzki S, Golan I et al (2002) CD44 in cancer. Crit Rev Clin Lab Sci 39:527–579

    Article  PubMed  CAS  Google Scholar 

  9. Jin L, Hope K, Zhai Q et al (2006) Targeting of CD44 eradicates human acute myeloid leukemic stem cells. Nat Med 12:1167–1174

    Article  PubMed  Google Scholar 

  10. Leung EL, Fiscus RR, Tung JW et al (2010) Non-small cell lung cancer cells expressing CD44 are enriched for stem cell-like properties. PLoS ONE 5:e14062

    Article  PubMed  Google Scholar 

  11. Haraguchi N, Ohkuma M, Sakashita H et al (2008) CD133+ CD44+ population efficiently enriches colon cancer initiating cells. Ann Surg Oncol 15(10):2927–2933

    Article  PubMed  Google Scholar 

  12. Jothy S (2003) CD44 and its partners in metastasis. Clin Exp Metastasis 20:195–201

    Article  PubMed  CAS  Google Scholar 

  13. Seiter S, Schadendorf D, Herrmann K et al (1996) Expression of CD44 variant isoforms in malignant melanoma. Clin Cancer Res 2:447–456

    PubMed  CAS  Google Scholar 

  14. Akisik E, Bavbek S, Dalay N (2002) CD44 variant exons in leukemia and lymphoma. Pathol Oncol Res 8:36–40

    Article  PubMed  CAS  Google Scholar 

  15. Endo K, Terada T (2000) Protein expression of CD44 (standard and variant isoforms) in hepatocellular carcinoma: relationships with tumor grade, clinicopathologic parameters, p53 expression, and patient survival. J Hepatol 32:78–84

    Article  PubMed  CAS  Google Scholar 

  16. Iizuka N, Oka M, Yamada-Okabe H et al (2003) Oligonucleotide microarray for prediction of early intrahepatic recurrence of hepatocellular carcinoma after curative resection. Lancet 361:923–929

    Article  PubMed  CAS  Google Scholar 

  17. Wang SM, Ooi LL, Hui KM (2007) Identification and validation of a novel gene signature associated with the recurrence of human hepatocellular carcinoma. Clin Cancer Res 13:6275–6283

    Article  PubMed  CAS  Google Scholar 

  18. Woo HG, Park ES, Cheon JH et al (2008) Gene expression-based recurrence prediction of hepatitis B virus-related human hepatocellular carcinoma. Clin Cancer Res 14:2056–2064

    Article  PubMed  CAS  Google Scholar 

  19. Poon RT, Fan ST, Ng IO et al (2000) Different risk factors and prognosis for early and late intrahepatic recurrence after resection of hepatocellular carcinoma. Cancer 89:500–507

    Article  PubMed  CAS  Google Scholar 

  20. Kumada T, Nakano S, Takeda I et al (1997) Patterns of recurrence after initial treatment in patients with small hepatocellular carcinoma. Hepatology 25:87–92

    Article  PubMed  CAS  Google Scholar 

  21. Utsunomiya T, Okamoto M, Wakiyama S et al (2006) Specific gene-expression profiles of noncancerous liver tissue predict the risk for multicentric occurrence of hepatocellular carcinoma in hepatitis C virus-positive patients. Ann Surg Oncol 13:947–954

    Article  PubMed  Google Scholar 

  22. Utsunomiya T, Shimada M, Imura S et al (2010) Molecular signatures of noncancerous liver tissue can predict the risk for late recurrence of hepatocellular carcinoma. J Gastroenterol 45:146–152

    Article  PubMed  CAS  Google Scholar 

  23. Kim HR, Wheeler MA, Wilson CM et al (2004) Hyaluronan facilitates invasion of colon carcinoma cells in vitro via interaction with CD44. Cancer Res 64(13):4569–4576

    Article  PubMed  CAS  Google Scholar 

  24. Zöller M (2011) CD44: can a cancer-initiating cell profit from an abundantly expressed molecule? Nat Rev Cancer 11(4):254–267

    Article  PubMed  Google Scholar 

  25. Marhaba R, Klingbeil P, Nuebel T et al (2008) CD44 and EpCAM: cancer-initiating cell markers. Curr Mol Med 8(8):784–804

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported in part by Grants-in-Aid for Scientific Research (B) (20390359) and for Scientific Research (C) (22591506), and Grant-in-Aid for Challenging Exploratory Research (22659233 and 22659243), Japan Society for the Promotion of Science. This work was also supported in part by a grant from the Cancer Research Project Cooperated by TAIHO Pharmaceutical Co., LTD., and the University of Tokushima.

Conflict of interest

All authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Satoru Imura.

About this article

Cite this article

Tovuu, LO., Imura, S., Utsunomiya, T. et al. Role of CD44 expression in non-tumor tissue on intrahepatic recurrence of hepatocellular carcinoma. Int J Clin Oncol 18, 651–656 (2013). https://doi.org/10.1007/s10147-012-0432-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10147-012-0432-6

Keywords

Navigation