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

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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

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Abbreviations

5FU:

5-Fluorouracil

DPD:

Dihydropyrimidine dehydrogenase

HCC:

Hepatocellular carcinoma

IFNR2:

Interferon-receptor 2

NR:

Nonresponder

OS:

Overall survival

PD:

Progressive disease

PEG-IFN:

Pegylated interferon

PFS:

Progression-free survival

PR:

Partial response

RR:

Response rate

SD:

Stable disease

TS:

Thymidylate synthase

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Acknowledgments

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

Conflict of interest

None.

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Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kinki University School of Medicine, 377-2 Ohno-Higashi, Ōsakasayama, Osaka, 589-8511, Japan

    Satoru Hagiwara, Masatoshi Kudo, Kazuomi Ueshima, Hobyung Chung, Mami Yamaguchi & Masahiro Takita

  2. Department of Surgery, Kinki University School of Medicine, Ōsakasayama, Japan

    Seiji Haji

  3. Department of Pathology, Kinki University School of Medicine, Ōsakasayama, Japan

    Masatomo Kimura

  4. Department of Genome Biology, Kinki University School of Medicine, Ōsakasayama, Japan

    Tokuzo Arao & Kazuto Nishio

  5. Department of Biochemistry, Kinki University School of Medicine, Ōsakasayama, Japan

    Ah-Mee Park & Hiroshi Munakata

Authors
  1. Satoru Hagiwara
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  2. Masatoshi Kudo
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  3. Kazuomi Ueshima
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Correspondence to Masatoshi Kudo.

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Hagiwara, S., Kudo, M., Ueshima, K. et al. The cancer stem cell marker CD133 is a predictor of the effectiveness of S1+ pegylated interferon α-2b therapy against advanced hepatocellular carcinoma. J Gastroenterol 46, 212–221 (2011). https://doi.org/10.1007/s00535-010-0294-5

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  • DOI: https://doi.org/10.1007/s00535-010-0294-5

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