Tumor Biology

, Volume 36, Issue 7, pp 4973–4978 | Cite as

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

  • Rattaya Amornpisutt
  • Siriporn Proungvitaya
  • Patcharee Jearanaikoon
  • Temduang Limpaiboon
Research Article

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.

Keywords

Biliary tract cancer Liver cancer Methylation-sensitive high-resolution melting DNA methylation Biomarkers 

Notes

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.

Conflicts of interest

None

Supplementary material

13277_2015_3147_MOESM1_ESM.docx (976 kb)
Fig. S1 (DOCX 976 kb)
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Fig. S2 (DOCX 1002 kb)
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Table S1 (DOCX 17 kb)
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Table S2 (DOCX 18 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Rattaya Amornpisutt
    • 1
  • Siriporn Proungvitaya
    • 1
    • 2
  • Patcharee Jearanaikoon
    • 1
    • 2
  • Temduang Limpaiboon
    • 1
    • 2
  1. 1.Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical SciencesKhon Kaen UniversityKhon KaenThailand
  2. 2.Liver Fluke and Cholangiocarcinoma Research Center, Faculty of MedicineKhon Kaen UniversityKhon KaenThailand

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