Bile-Based Detection of Extrahepatic Cholangiocarcinoma with Quantitative DNA Methylation Markers and Its High Sensitivity

被引：41

作者：

Shin, So-Hyun ^{[4
]}

Lee, Kyoungbun ^{[1
]}

Kim, Baek-Hui ^{[5
]}

Cho, Nam-Yun ^{[4
]}

Jang, Jin-Young ^{[2
]}

Kim, Yong-Tae ^{[3
]}

Kim, Donguk ^{[6
]}

Jang, Ja June ^{[1
]}

Kang, Gyeong Hoon ^{[1
,4
]}

机构：

[1] Seoul Natl Univ, Coll Med, Dept Pathol, Seoul 110744, South Korea

[2] Seoul Natl Univ, Coll Med, Dept Gen Surg, Seoul 110744, South Korea

[3] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 110744, South Korea

[4] Seoul Natl Univ, Coll Med, Canc Res Inst, Lab Epigenet, Seoul 110744, South Korea

[5] Korea Univ, Sch Med, Dept Pathol, Seoul, South Korea

[6] Sungkyunkwan Univ, Dept Stat, Seoul, South Korea

来源：

JOURNAL OF MOLECULAR DIAGNOSTICS | 2012年 / 14卷 / 03期

基金：

新加坡国家研究基金会;

关键词：

BILIARY-TRACT CANCERS; PROMOTER METHYLATION; COLORECTAL-CANCER; O-6-METHYLGUANINE-DNA METHYLTRANSFERASE; GASTRIC MUCOSAE; MULTIPLE GENES; BRUSH CYTOLOGY; HYPERMETHYLATION; CARCINOMA; DIAGNOSIS;

D O I：

10.1016/j.jmoldx.2012.01.014

中图分类号：

R36 [病理学];

学科分类号：

100104 ;

摘要：

Extrahepatic cholangiocarcinoma (EHC) is usually difficult to diagnose by bile cytology because of cellular disintegration. However, DNA samples from bile fluid can provide sufficient materials to screen for the presence of EHC. We developed DNA methylation marker panels that can be used for MethyLight assay-based detection of EHC in bile fluid specimens. The methylation status of 59 DNA methylation markers was investigated in 20 EHC and 20 non-neoplastic gallbladder tissue samples with MethyLight assay to determine cancer-specific DNA methylation markers. Through assaying cancer-specific DNA methylation markers in a training set (n = 40) and validation set (n = 45) of bile fluid specimens from patients with EHC or those without cancer, we selected suitable marker panels that were assessed for their performance in a third set (test set; n = 40). Four marker panels showed a sensitivity of 60010 or more and a specificity of 100% In both the training and validation sets, whereas bile cytology displayed a sensitivity of 40% to 46% and a specificity of 100%. In an independent test set of bile fluid samples, a five-gene panel (CCND2, CDH13, GRIN2B, RUNX3, and TWIST1) detected EHC at a sensitivity of 83%, which was far higher than that of bile cytology (46%, P = 0.004). Using bile fluids, a methylation assay consisting of a five-gene panel may be useful for detecting EHC and in helping to increase the sensitivity of preoperative diagnoses. (J Mol Diagn 2012, 14:256-263; DOI: 10.1016/j.jmoldx.2012.01.014)

引用

页码：256 / 263

页数：8