Bile-based detection of extrahepatic cholangiocarcinoma with quantitative DNA methylation markers and its high sensitivity

So Hyun Shin, Kyoungbun Lee, Baek-Hui Kim, Nam Yun Cho, Jin Young Jang, Yong Tae Kim, Donguk Kim, Ja June Jang, Gyeong Hoon Kang

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

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 60% 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.

Original languageEnglish
Pages (from-to)256-263
Number of pages8
JournalJournal of Molecular Diagnostics
Volume14
Issue number3
DOIs
Publication statusPublished - 2012 May 1

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Cholangiocarcinoma
DNA Methylation
Genetic Markers
Bile
Cell Biology
Methylation
Neoplasms
Gallbladder
Genes
DNA

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Medicine

Cite this

Bile-based detection of extrahepatic cholangiocarcinoma with quantitative DNA methylation markers and its high sensitivity. / Shin, So Hyun; Lee, Kyoungbun; Kim, Baek-Hui; Cho, Nam Yun; Jang, Jin Young; Kim, Yong Tae; Kim, Donguk; Jang, Ja June; Kang, Gyeong Hoon.

In: Journal of Molecular Diagnostics, Vol. 14, No. 3, 01.05.2012, p. 256-263.

Research output: Contribution to journalArticle

Shin, So Hyun ; Lee, Kyoungbun ; Kim, Baek-Hui ; Cho, Nam Yun ; Jang, Jin Young ; Kim, Yong Tae ; Kim, Donguk ; Jang, Ja June ; Kang, Gyeong Hoon. / Bile-based detection of extrahepatic cholangiocarcinoma with quantitative DNA methylation markers and its high sensitivity. In: Journal of Molecular Diagnostics. 2012 ; Vol. 14, No. 3. pp. 256-263.
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