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The complement component C3a fragment is a potential biomarker for hepatitis C virus-related hepatocellular carcinoma

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
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Abstract

Background

Hepatocellular carcinoma (HCC) has a high mortality rate, and early detection of HCC improves patient survival. However, the molecular diagnostic markers for early HCC have not been fully elucidated. The aim of this study was to identify novel diagnostic markers for HCC.

Methods

Serum protein profiles of 45 hepatitis C virus infection (HCV)-related HCC patients (HCV-HCC) were compared to 42 HCV-related chronic liver disease patients without HCC (HCV-CLD) and 21 healthy volunteers using the ProteinChip SELDI system. One of the identified proteins was evaluated as a diagnostic marker for HCC in patients with HCV.

Results

Five protein peaks (4067, 4470, 7564, 7929, and 8130 m/z) had p-values less than 1 × 10−7 and were significantly increased in the sera of HCV-HCC patients compared to HCV-CLD patients and healthy volunteers. Among these proteins, an 8130 m/z peak was the most differentially expressed and identified as the complement component 3a (C3a) fragment. For HCV-HCC and HCV-CLD, the relative intensity of this C3a fragment had the best area under the ROC curve [0.70], followed by des-γ-carboxy prothrombin (DCP) [0.68], lectin-bound alpha fetoprotein (AFP-L3) [0.58] and AFP [0.53] for HCC. A combined analysis of the C3a fragment, AFP and DCP led to a 98% positive identification rate. In addition, the measurable C3a fragment in some HCC patients was not only significantly higher in the year of HCC onset compared to the pre-onset year, but also decreased after treatment.

Conclusions

The 8130 m/z C3a fragment is a potential marker for the early detection of HCV-related HCC.

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Acknowledgments

We thank Mr. Hiroyuki Nakao for assistance with the statistical analyses. We also thank Ms. Yuko Morinaga for her technical assistance. This work was supported in part by a grant-in-aid from the Collaboration of Regional Entities for the Advancement of Technological Excellence (CREATE) from the Japan Science and Technology Agency, a grant (no. CA87982) from the United States National Institutes of Health, and a grant-in-aid (Research on Hepatitis and BSE) from the Ministry of Health, Labour and Welfare of Japan.

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Authors and Affiliations

  1. Digestive Disease and Life-style Related Disease Health Research, Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan

    Shuji Kanmura, Hirofumi Uto, Koutarou Kumagai, Fumisato Sasaki, Akihiro Moriuchi, Makoto Oketani, Akio Ido & Hirohito Tsubouchi

  2. Miyazaki Prefectual Industrial Support Foundation, Miyazaki, Japan

    Yuko Sato

  3. Division of Gastroenterology and Hematology, Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan

    Kenji Nagata

  4. Faculty of Medicine, Center for Medical Education, University of Miyazaki, Miyazaki, Japan

    Katsuhiro Hayashi

  5. Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA

    Sherri O. Stuver

  6. Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA

    Sherri O. Stuver

Authors
  1. Shuji Kanmura
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  2. Hirofumi Uto
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  9. Kenji Nagata
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  12. Hirohito Tsubouchi
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Correspondence to Hirofumi Uto.

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Kanmura, S., Uto, H., Sato, Y. et al. The complement component C3a fragment is a potential biomarker for hepatitis C virus-related hepatocellular carcinoma. J Gastroenterol 45, 459–467 (2010). https://doi.org/10.1007/s00535-009-0160-5

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  • DOI: https://doi.org/10.1007/s00535-009-0160-5

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