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Increase of exostosin 1 in plasma as a potential biomarker for opisthorchiasis-associated cholangiocarcinoma

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Tumor Biology

Abstract

A proteomic-based approach was used to search for potential markers in the plasma of hamsters in which cholangiocarcinoma (CCA) was induced by Opisthorchis viverrini infection and N-nitrosodimethylamine treatment. The plasma proteins of CCA-induced hamsters were resolved by 1-D PAGE, digested by trypsin, and analyzed by LC-MS/MS. From the criteria of protein ID scores >15 and an overexpression of at least three times across all time points, 37 proteins were selected. These overexpressed proteins largely consisted of signal transduction, structural, transport, and transcriptional proteins in the order. Among the most frequently upregulated proteins, exostosin 1 (EXT1) was selected for further validation. By western blot analysis, the EXT1 expression level in the plasma of hamster CCA was significantly higher than that of controls at 1 month and thereafter. Immunohistochemistry revealed that EXT1 was expressed at vascular walls and fibroblasts at 21 days (before tumor onset) and at 2 months (early CCA) posttreatment. Its expression was also observed in bile duct cancer cells during tumor progression at 6 months posttreatment. In the human CCA tissue microarray, EXT1 immunoreactivity was found not only in vascular walls and fibroblasts but also in bile duct cancer cells and was positive in 89.7 % (61/68) of the cases. By ELISA and immunoblotting, plasma EXT1 level was significantly higher in human CCA compared to healthy controls. In conclusion, these results suggest that increased expression of EXT1 level in the plasma might be involved in CCA genesis and might be a potential biomarker of CCA.

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Abbreviations

OV:

Opisthorchis viverrini

CCA:

Cholangiocarcinoma

EXT1:

Exostosin 1

ECM:

Extracellular matrix

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Acknowledgments

This work was supported by The Thailand Research Fund through the Royal Golden Jubilee Ph.D. Program (to JK and SP), Thailand Research Fund (RMU5380016), a Research Team Strengthening Grant from BIOTEC-NSTDA, Thailand, The Invitation Research from the Faculty of Medicine, Khon Kaen University, Thailand, and The Higher Education Research Promotion and National Research University Project of Thailand, Office of the Higher Education Commission, through the Health Cluster (SHeP-GMS), Khon Kaen University, Thailand. We thank a Research Assistant, Faculty of Medicine, Khon Kaen University, Thailand, for the technical support. We wish to acknowledge the support of the Khon Kaen University Publication Clinic, Research and Technology Transfer Affairs, Khon Kaen University, for their assistance. We also thank Prof. Yukifumi Nawa, Research Affairs, Faculty of Medicine, Khon Kaen University, Thailand, for his suggestion and critical reading of the manuscript.

Conflicts of interest

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Authors and Affiliations

  1. Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand

    Jarinya Khoontawad, Nuttanan Hongsrichan, Thidarut Boonmars & Somchai Pinlaor

  2. Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand

    Yaovalux Chamgramol & Chawalit Pairojkul

  3. Centre for Research and Development in Medical Diagnostic Laboratory, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, 40002, Thailand

    Porntip Pinlaor

  4. Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand

    Chaisiri Wongkham & Puangrat Yongvanit

  5. Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand

    Narong Khuntikeo

  6. Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand

    Jarinya Khoontawad, Nuttanan Hongsrichan, Yaovalux Chamgramol, Porntip Pinlaor, Chaisiri Wongkham, Puangrat Yongvanit, Chawalit Pairojkul, Narong Khuntikeo, Thidarut Boonmars & Somchai Pinlaor

  7. Proteomics Research Laboratory, Genome Institute Biotechnology, Pathum Thani, 12120, Thailand

    Sittiruk Roytrakul

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  1. Jarinya Khoontawad
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  2. Nuttanan Hongsrichan
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  7. Chawalit Pairojkul
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Corresponding author

Correspondence to Somchai Pinlaor.

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Khoontawad, J., Hongsrichan, N., Chamgramol, Y. et al. Increase of exostosin 1 in plasma as a potential biomarker for opisthorchiasis-associated cholangiocarcinoma. Tumor Biol. 35, 1029–1039 (2014). https://doi.org/10.1007/s13277-013-1137-9

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  • DOI: https://doi.org/10.1007/s13277-013-1137-9

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