Journal of Gastroenterology

, Volume 46, Issue 2, pp 212–221 | Cite as

The cancer stem cell marker CD133 is a predictor of the effectiveness of S1+ pegylated interferon α-2b therapy against advanced hepatocellular carcinoma

  • Satoru Hagiwara
  • Masatoshi KudoEmail author
  • Kazuomi Ueshima
  • Hobyung Chung
  • Mami Yamaguchi
  • Masahiro Takita
  • Seiji Haji
  • Masatomo Kimura
  • Tokuzo Arao
  • Kazuto Nishio
  • Ah-Mee Park
  • Hiroshi Munakata
Original Article—Liver, Pancreas, and Biliary Tract



Combination therapy with the oral fluoropyrimidine anticancer drug S1 and interferon is reportedly effective for the treatment of advanced hepatocellular carcinoma (HCC), but selection criteria for this therapy have not been clarified. In this study, we attempted to identify factors predicting the effectiveness of this combination therapy.


Pathological specimens of HCC were collected before treatment from 31 patients with advanced HCC who underwent S1+ pegylated-interferon (PEG-IFN) α-2b therapy between January 2007 and January 2009. In these pathological specimens, the expression levels of CD133, thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and interferon-receptor 2 (IFNR2) proteins were determined by Western blot assay. The presence or absence of p53 gene mutations was determined by direct sequencing. The relationships between these protein expression levels and the response rate (RR), progression-free survival (PFS), and overall survival (OS) were evaluated.


The CD133 protein expression level was significantly lower in the responder group than in the nonresponder group. Comparing the PFS and OS between high- and low-level CD133 expression groups (n = 13 and 18, respectively) revealed that both parameters were significantly prolonged in the latter group. The expression levels of TS, DPD, and IFNR2 protein and the presence of p53 gene mutations did not correlate with the RR.


CD133 was identified as a predictor of the therapeutic effect of S1+ PEG-IFN α-2b therapy against advanced HCC.


5-Fluorouracil Pegylated interferon CD133 Cancer stem cell Hepatocellular carcinoma 





Dihydropyrimidine dehydrogenase


Hepatocellular carcinoma


Interferon-receptor 2




Overall survival


Progressive disease


Pegylated interferon


Progression-free survival


Partial response


Response rate


Stable disease


Thymidylate synthase



The protocol of this study was approved by the Medical Committee of Kinki University of Medicine.

Conflict of interest



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Copyright information

© Springer 2010

Authors and Affiliations

  • Satoru Hagiwara
    • 1
  • Masatoshi Kudo
    • 1
    Email author
  • Kazuomi Ueshima
    • 1
  • Hobyung Chung
    • 1
  • Mami Yamaguchi
    • 1
  • Masahiro Takita
    • 1
  • Seiji Haji
    • 2
  • Masatomo Kimura
    • 3
  • Tokuzo Arao
    • 4
  • Kazuto Nishio
    • 4
  • Ah-Mee Park
    • 5
  • Hiroshi Munakata
    • 5
  1. 1.Division of Gastroenterology and Hepatology, Department of Internal MedicineKinki University School of MedicineŌsakasayamaJapan
  2. 2.Department of SurgeryKinki University School of MedicineŌsakasayamaJapan
  3. 3.Department of PathologyKinki University School of MedicineŌsakasayamaJapan
  4. 4.Department of Genome BiologyKinki University School of MedicineŌsakasayamaJapan
  5. 5.Department of BiochemistryKinki University School of MedicineŌsakasayamaJapan

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