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High CD44s expression is associated with the EMT expression profile and intrahepatic dissemination of hepatocellular carcinoma after local ablation therapy

  • Original article
  • Published:
Journal of Hepato-Biliary-Pancreatic Sciences

Abstract

Background/purpose

Local ablation therapy (LAT) is a widely used treatment for hepatocellular carcinoma (HCC) because it is less invasive than hepatic resection. The precise molecular mechanism underlying local HCC recurrence after LAT is largely unknown. The CD44 standard isoform (CD44s) is involved in epithelial–mesenchymal transition (EMT) in HCC. We investigate the significance of CD44s expression and EMT expression profile in local HCC recurrence after LAT.

Methods

We studied the expression levels of CD44s, EMT expression profile (E-cadherinlow/vimentinhigh expression) and their association with clinicopathological factors in 30 HCC samples from patients with locally recurrent HCCs after LAT following hepatic resection. The alterations of CD44s expression was compared with those in initial HCCs from 150 patients without prior any anticancer treatment including LAT.

Results

A high CD44s expression was significantly associated with the EMT expression profile (P = 0.002), and it was also detected with a higher frequency in the locally recurrent HCCs after LAT compared to initial HCCs (P < 0.001). In addition, high CD44s expression was associated with the intrahepatic dissemination of HCC after LAT (P = 0.006).

Conclusions

These results suggest that high CD44s expression is associated with the aggressive recurrence pattern via EMT after LAT for HCC.

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References

  1. El-Serag HB. Hepatocellular carcinoma. N Engl J Med. 2011;365:1118–27.

    Article  PubMed  CAS  Google Scholar 

  2. Poon RT, Ng IO, Fan ST, Lai EC, Lo CM, Liu CL, et al. Clinicopathologic features of long-term survivors and disease-free survivors after resection of hepatocellular carcinoma: a study of a prospective cohort. J Clin Oncol. 2001;19:3037–44.

    PubMed  CAS  Google Scholar 

  3. Poon RT, Fan ST, Tsang FH, Wong J. Locoregional therapies for hepatocellular carcinoma: a critical review from the surgeon’s perspective. Ann Surg. 2002;235:466–86.

    Article  PubMed  Google Scholar 

  4. Tiong L, Maddern GJ. Systematic review and meta-analysis of survival and disease recurrence after radiofrequency ablation for hepatocellular carcinoma. Br J Surg. 2011;98:1210–24.

    Article  PubMed  CAS  Google Scholar 

  5. Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelial–mesenchymal transitions in development and disease. Cell. 2009;139:871–90.

    Article  PubMed  CAS  Google Scholar 

  6. Moody SE, Perez D, Pan TC, Sarkisian CJ, Portocarrero CP, Sterner CJ, et al. The transcriptional repressor Snail promotes mammary tumor recurrence. Cancer Cell. 2005;8:197–209.

    Article  PubMed  CAS  Google Scholar 

  7. Shioiri M, Shida T, Koda K, Oda K, Seike K, Nishimura M, et al. Slug expression is an independent prognostic parameter for poor survival in colorectal carcinoma patients. Br J Cancer. 2006;94:1816–22.

    Article  PubMed  CAS  Google Scholar 

  8. Ponta H, Sherman L, Herrlich PA. CD44: from adhesion molecules to signalling regulators. Nat Rev Mol Cell Biol. 2003;4:33–45.

    Article  PubMed  CAS  Google Scholar 

  9. Zoller M. CD44: can a cancer-initiating cell profit from an abundantly expressed molecule? Nat Rev Cancer. 2011;11:254–67.

    Article  PubMed  Google Scholar 

  10. Mima K, Okabe H, Ishimoto T, Hayashi H, Nakagawa S, Kuroki H, et al. CD44s regulates the TGF-beta-mediated mesenchymal phenotype and is associated with poor prognosis in patients with hepatocellular carcinoma. Cancer Res. 2012;72:3414–23.

    Article  PubMed  CAS  Google Scholar 

  11. Dodd GD 3rd, Frank MS, Aribandi M, Chopra S, Chintapalli KN. Radiofrequency thermal ablation: computer analysis of the size of the thermal injury created by overlapping ablations. AJR Am J Roentgenol. 2001;177:777–82.

    Article  PubMed  Google Scholar 

  12. Masuda T, Beppu T, Ishiko T, Horino K, Baba Y, Mizumoto T, et al. Intrahepatic dissemination of hepatocellular carcinoma after local ablation therapy. J Hepatobiliary Pancreat Surg. 2008;15:589–95.

    Article  PubMed  Google Scholar 

  13. The Liver Cancer Study Group of Japan. The General Rules for the Clinical and Pathological Study of Primary Liver Cancer. The 5th Edition, Revised Version ed. Tokyo: Kanehara; 2009.

  14. Minagawa M, Ikai I, Matsuyama Y, Yamaoka Y, 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. 2007;245:909–22.

    Article  PubMed  Google Scholar 

  15. Vauthey JN, Lauwers GY, Esnaola NF, Do KA, Belghiti J, Mirza N, et al. Simplified staging for hepatocellular carcinoma. J Clin Oncol. 2002;20:1527–36.

    Article  PubMed  Google Scholar 

  16. Llovet JM, Vilana R, Bru C, Bianchi L, Salmeron JM, Boix L, et al. Increased risk of tumor seeding after percutaneous radiofrequency ablation for single hepatocellular carcinoma. Hepatology. 2001;33:1124–9.

    Article  PubMed  CAS  Google Scholar 

  17. Poon RT, Lau C, Pang R, Ng KK, Yuen J, Fan ST. High serum vascular endothelial growth factor levels predict poor prognosis after radiofrequency ablation of hepatocellular carcinoma: importance of tumor biomarker in ablative therapies. Ann Surg Oncol. 2007;14:1835–45.

    Article  PubMed  Google Scholar 

  18. Tsuchiya K, Komuta M, Yasui Y, Tamaki N, Hosokawa T, Ueda K, et al. Expression of keratin 19 is related to high recurrence of hepatocellular carcinoma after radiofrequency ablation. Oncology. 2011;80:278–88.

    Article  PubMed  CAS  Google Scholar 

  19. Xia F, Lai EC, Lau WY, Ma K, Li X, Bie P, et al. High serum hyaluronic acid and HBV viral load are main prognostic factors of local recurrence after complete radiofrequency ablation of hepatitis B-related small hepatocellular carcinoma. Ann Surg Oncol. 2012;19:1284–91.

    Article  PubMed  Google Scholar 

  20. Ahmad F, Gravante G, Bhardwaj N, Strickland A, Basit R, West K, et al. Changes in interleukin-1beta and 6 after hepatic microwave tissue ablation compared with radiofrequency, cryotherapy and surgical resections. Am J Surg. 2010;200:500–6.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank Keisuke Miyake and Naoko Yokoyama for their valuable technical assistance.

Conflict of interest

The authors declare that they have no conflict of interest.

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Corresponding author

Correspondence to Hideo Baba.

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Mima, K., Hayashi, H., Imai, K. et al. High CD44s expression is associated with the EMT expression profile and intrahepatic dissemination of hepatocellular carcinoma after local ablation therapy. J Hepatobiliary Pancreat Sci 20, 429–434 (2013). https://doi.org/10.1007/s00534-012-0580-0

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  • DOI: https://doi.org/10.1007/s00534-012-0580-0

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