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.

Promoter hypermethylation of SHOX2 and SEPT9 is a potential biomarker for minimally invasive diagnosis in adenocarcinomas of the biliary tract

“…In order to overcome the low sensitivity, other biomarkers could be added to the panel. A recent study identified DNA methylation level of OPCML and SFRP1 as a potential diagnostic biomarker in BTC [58]. The AUC value of OPCML was 0.932 and of SFRP1 was 0.951.…”

Epigenetic biomarkers of promoter DNA methylation in the new era of cancer treatment

“…Liquid biopsy using such HRMG showed superior diagnosis (73%‐91%) and high specificity (95%‐100%) compared to the conventional cytology test (58%‐63%). Recently, additional HRMG with high performance have been identified, including SFRP1 , OPCML and SHOX2 (Table ), and additional optimization of the HRMG analyses may yield further improvements in performance.…”

Aberrant gene-specific DNA methylation signature analysis in cervical cancer

“…7 In addition to their role in transcription silencing and tumor development, the hypermethylation of promoters at specific CpG sites can be sensitive and specific diagnostic and prognostic markers. 8,9 For example, DNA promoter methylation of glutathione S-transferase pi 1 (GSTP1) and O-6-methylguanine-DNA methyltransferase (MGMT1) is reported as a potential diagnostic marker for glioblastoma and prostate cancer. [10][11][12] It has been shown that 95% of the adenocarcinoma of the prostate have methylated GSTP1 promoter, while the normal tissues were apparently negative.…”