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DNA methylation level of OPCML and SFRP1: a potential diagnostic biomarker of cholangiocarcinoma

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Tumor Biology

Abstract

Cholangiocarcinoma (CCA) is a malignancy of the bile duct epithelium which is caused by liver fluke infection. The clinical symptoms of CCA were revealed as the disease progresses to advanced stage. Thus, specific diagnostic biomarkers are important for this fatal disease. We applied methylation-sensitive high-resolution melting (MS-HRM) to quantify DNA methylation levels of opioid binding protein/cell adhesion molecule-like gene (OPCML) and Secreted frizzled-related protein 1 (SFRP1) in 73 primary CCA and 10 adjacent normal tissues and evaluated the sensitivity, specificity, and accuracy of the assay. The median methylation level of OPCML in CCA was 38.7 % (ranged from 0 to 82.2 %) and of SFRP1 was 31.5 % (ranged from 0 to 86.2 %). Methylation cutoff values of OPCML and SFRP1 derived from adjacent normal tissue were 6.90 and 10.44 %, respectively. With these cutoff values, the area under curve (AUC) of OPCML was 0.932 (95 % CI 0.878–0.986) and of SFRP1 was 0.951 (95 % CI 0.905–0.996). The sensitivity, specificity, and accuracy of OPCML were 89.04, 100, and 90.36 %, respectively, and of SFRP1 were 83.56, 100, and 85.54 %, respectively. In conclusion, the DNA methylation levels of OPCML and SFRP1 could be potential biomarkers for diagnosis of CCA with high specificity, sensitivity, and accuracy, in particular for biopsy specimens. Further validation in noninvasive samples such as serum or plasma is warranted for clinical applicability, especially as early diagnostic biomarkers.

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Acknowledgments

This work was supported by Khon Kaen University Research Affairs under the National Research Council of Thailand. R.A. was granted by the Centre for Research and Development of Medical Diagnostic Laboratories (CMDL), Faculty of Associated Medical Sciences; and Graduate School, Khon Kaen University. We thank the Liver Fluke and Cholangiocarcinoma Research Center for clinical specimens and data.

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Authors and Affiliations

  1. Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, 40002, Thailand

    Rattaya Amornpisutt, Siriporn Proungvitaya, Patcharee Jearanaikoon & Temduang Limpaiboon

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

    Siriporn Proungvitaya, Patcharee Jearanaikoon & Temduang Limpaiboon

Authors
  1. Rattaya Amornpisutt
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  2. Siriporn Proungvitaya
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  4. Temduang Limpaiboon
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Correspondence to Temduang Limpaiboon.

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Amornpisutt, R., Proungvitaya, S., Jearanaikoon, P. et al. DNA methylation level of OPCML and SFRP1: a potential diagnostic biomarker of cholangiocarcinoma. Tumor Biol. 36, 4973–4978 (2015). https://doi.org/10.1007/s13277-015-3147-2

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  • DOI: https://doi.org/10.1007/s13277-015-3147-2

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