title: DNA methylation level of OPCML and SFRP1: a potential diagnostic biomarker of cholangiocarcinoma.
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.
authors: Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, 40002, Thailand.
authors: Rattaya
authors: R
authors: Amornpisutt
authors: Siriporn
authors: S
authors: Proungvitaya
authors: Patcharee
authors: P
authors: Jearanaikoon
authors: Temduang
authors: T
authors: Limpaiboon
mesh_terms: D000818:Animals; D001661:Biliary Tract Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000235:genetics*; D018281:Cholangiocarcinoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation / Q000235:genetics*; D005210:Fasciola hepatica / Q000235:genetics; D058851:GPI-Linked Proteins / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D009691:Nucleic Acid Denaturation / Q000235:genetics; D012372:ROC Curve; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C059785:OPCML protein, human; C117636:SFRP1 protein, human; D000094742:Secreted Frizzled-Related Proteins
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