Sensitive and Specific Detection of Early Gastric Cancer with DNA Methylation Analysis of Gastric Washes

Yoshiyuki Watanabe, Hyun Soo Kim, Ryan J. Castoro, Woonbok Chung, Marcos R.H. Estecio, Kimie Kondo, Yi Guo, Saira S. Ahmed, Minoru Toyota, Fumio Itoh, Ki Tae Suk, Meeyon Cho, Lanlan Shen, Jaroslav Jelinek, Jean Pierre J. Issa

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

Background & Aims: Aberrant DNA methylation is an early and frequent process in gastric carcinogenesis and could be useful for detection of gastric neoplasia. We hypothesized that methylation analysis of DNA recovered from gastric washes could be used to detect gastric cancer. Methods: We studied 51 candidate genes in 7 gastric cancer cell lines and 24 samples (training set) and identified 6 for further studies. We examined the methylation status of these genes in a test set consisting of 131 gastric neoplasias at various stages. Finally, we validated the 6 candidate genes in a different population of 40 primary gastric cancer samples and 113 nonneoplastic gastric mucosa samples. Results: Six genes (MINT25, RORA, GDNF, ADAM23, PRDM5, MLF1) showed frequent differential methylation between gastric cancer and normal mucosa in the training, test, and validation sets. GDNF and MINT25 were most sensitive molecular markers of early stage gastric cancer, whereas PRDM5 and MLF1 were markers of a field defect. There was a close correlation (r = 0.5-0.9, P = .03-.001) between methylation levels in tumor biopsy and gastric washes. MINT25 methylation had the best sensitivity (90%), specificity (96%), and area under the receiver operating characteristic curve (0.961) in terms of tumor detection in gastric washes. Conclusions: These findings suggest MINT25 is a sensitive and specific marker for screening in gastric cancer. Additionally, we have developed a new method for gastric cancer detection by DNA methylation in gastric washes.

Original languageEnglish
Pages (from-to)2149-2158
Number of pages10
JournalGastroenterology
Volume136
Issue number7
DOIs
Publication statusPublished - 2009 Jan 1

Fingerprint

DNA Methylation
Stomach Neoplasms
Stomach
Methylation
Glial Cell Line-Derived Neurotrophic Factor
Genes
Neoplasms
Gastric Mucosa
ROC Curve
Carcinogenesis
Mucous Membrane
Biopsy
Sensitivity and Specificity
Cell Line
Population

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

Cite this

Watanabe, Y., Kim, H. S., Castoro, R. J., Chung, W., Estecio, M. R. H., Kondo, K., ... Issa, J. P. J. (2009). Sensitive and Specific Detection of Early Gastric Cancer with DNA Methylation Analysis of Gastric Washes. Gastroenterology, 136(7), 2149-2158. https://doi.org/10.1053/j.gastro.2009.02.085
Watanabe, Yoshiyuki ; Kim, Hyun Soo ; Castoro, Ryan J. ; Chung, Woonbok ; Estecio, Marcos R.H. ; Kondo, Kimie ; Guo, Yi ; Ahmed, Saira S. ; Toyota, Minoru ; Itoh, Fumio ; Suk, Ki Tae ; Cho, Meeyon ; Shen, Lanlan ; Jelinek, Jaroslav ; Issa, Jean Pierre J. / Sensitive and Specific Detection of Early Gastric Cancer with DNA Methylation Analysis of Gastric Washes. In: Gastroenterology. 2009 ; Vol. 136, No. 7. pp. 2149-2158.
@article{3f324dc003f34789aef9c6b793d5cb6e,
title = "Sensitive and Specific Detection of Early Gastric Cancer with DNA Methylation Analysis of Gastric Washes",
abstract = "Background & Aims: Aberrant DNA methylation is an early and frequent process in gastric carcinogenesis and could be useful for detection of gastric neoplasia. We hypothesized that methylation analysis of DNA recovered from gastric washes could be used to detect gastric cancer. Methods: We studied 51 candidate genes in 7 gastric cancer cell lines and 24 samples (training set) and identified 6 for further studies. We examined the methylation status of these genes in a test set consisting of 131 gastric neoplasias at various stages. Finally, we validated the 6 candidate genes in a different population of 40 primary gastric cancer samples and 113 nonneoplastic gastric mucosa samples. Results: Six genes (MINT25, RORA, GDNF, ADAM23, PRDM5, MLF1) showed frequent differential methylation between gastric cancer and normal mucosa in the training, test, and validation sets. GDNF and MINT25 were most sensitive molecular markers of early stage gastric cancer, whereas PRDM5 and MLF1 were markers of a field defect. There was a close correlation (r = 0.5-0.9, P = .03-.001) between methylation levels in tumor biopsy and gastric washes. MINT25 methylation had the best sensitivity (90{\%}), specificity (96{\%}), and area under the receiver operating characteristic curve (0.961) in terms of tumor detection in gastric washes. Conclusions: These findings suggest MINT25 is a sensitive and specific marker for screening in gastric cancer. Additionally, we have developed a new method for gastric cancer detection by DNA methylation in gastric washes.",
author = "Yoshiyuki Watanabe and Kim, {Hyun Soo} and Castoro, {Ryan J.} and Woonbok Chung and Estecio, {Marcos R.H.} and Kimie Kondo and Yi Guo and Ahmed, {Saira S.} and Minoru Toyota and Fumio Itoh and Suk, {Ki Tae} and Meeyon Cho and Lanlan Shen and Jaroslav Jelinek and Issa, {Jean Pierre J.}",
year = "2009",
month = "1",
day = "1",
doi = "10.1053/j.gastro.2009.02.085",
language = "English",
volume = "136",
pages = "2149--2158",
journal = "Gastroenterology",
issn = "0016-5085",
publisher = "W.B. Saunders Ltd",
number = "7",

}

Watanabe, Y, Kim, HS, Castoro, RJ, Chung, W, Estecio, MRH, Kondo, K, Guo, Y, Ahmed, SS, Toyota, M, Itoh, F, Suk, KT, Cho, M, Shen, L, Jelinek, J & Issa, JPJ 2009, 'Sensitive and Specific Detection of Early Gastric Cancer with DNA Methylation Analysis of Gastric Washes', Gastroenterology, vol. 136, no. 7, pp. 2149-2158. https://doi.org/10.1053/j.gastro.2009.02.085

Sensitive and Specific Detection of Early Gastric Cancer with DNA Methylation Analysis of Gastric Washes. / Watanabe, Yoshiyuki; Kim, Hyun Soo; Castoro, Ryan J.; Chung, Woonbok; Estecio, Marcos R.H.; Kondo, Kimie; Guo, Yi; Ahmed, Saira S.; Toyota, Minoru; Itoh, Fumio; Suk, Ki Tae; Cho, Meeyon; Shen, Lanlan; Jelinek, Jaroslav; Issa, Jean Pierre J.

In: Gastroenterology, Vol. 136, No. 7, 01.01.2009, p. 2149-2158.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Sensitive and Specific Detection of Early Gastric Cancer with DNA Methylation Analysis of Gastric Washes

AU - Watanabe, Yoshiyuki

AU - Kim, Hyun Soo

AU - Castoro, Ryan J.

AU - Chung, Woonbok

AU - Estecio, Marcos R.H.

AU - Kondo, Kimie

AU - Guo, Yi

AU - Ahmed, Saira S.

AU - Toyota, Minoru

AU - Itoh, Fumio

AU - Suk, Ki Tae

AU - Cho, Meeyon

AU - Shen, Lanlan

AU - Jelinek, Jaroslav

AU - Issa, Jean Pierre J.

PY - 2009/1/1

Y1 - 2009/1/1

N2 - Background & Aims: Aberrant DNA methylation is an early and frequent process in gastric carcinogenesis and could be useful for detection of gastric neoplasia. We hypothesized that methylation analysis of DNA recovered from gastric washes could be used to detect gastric cancer. Methods: We studied 51 candidate genes in 7 gastric cancer cell lines and 24 samples (training set) and identified 6 for further studies. We examined the methylation status of these genes in a test set consisting of 131 gastric neoplasias at various stages. Finally, we validated the 6 candidate genes in a different population of 40 primary gastric cancer samples and 113 nonneoplastic gastric mucosa samples. Results: Six genes (MINT25, RORA, GDNF, ADAM23, PRDM5, MLF1) showed frequent differential methylation between gastric cancer and normal mucosa in the training, test, and validation sets. GDNF and MINT25 were most sensitive molecular markers of early stage gastric cancer, whereas PRDM5 and MLF1 were markers of a field defect. There was a close correlation (r = 0.5-0.9, P = .03-.001) between methylation levels in tumor biopsy and gastric washes. MINT25 methylation had the best sensitivity (90%), specificity (96%), and area under the receiver operating characteristic curve (0.961) in terms of tumor detection in gastric washes. Conclusions: These findings suggest MINT25 is a sensitive and specific marker for screening in gastric cancer. Additionally, we have developed a new method for gastric cancer detection by DNA methylation in gastric washes.

AB - Background & Aims: Aberrant DNA methylation is an early and frequent process in gastric carcinogenesis and could be useful for detection of gastric neoplasia. We hypothesized that methylation analysis of DNA recovered from gastric washes could be used to detect gastric cancer. Methods: We studied 51 candidate genes in 7 gastric cancer cell lines and 24 samples (training set) and identified 6 for further studies. We examined the methylation status of these genes in a test set consisting of 131 gastric neoplasias at various stages. Finally, we validated the 6 candidate genes in a different population of 40 primary gastric cancer samples and 113 nonneoplastic gastric mucosa samples. Results: Six genes (MINT25, RORA, GDNF, ADAM23, PRDM5, MLF1) showed frequent differential methylation between gastric cancer and normal mucosa in the training, test, and validation sets. GDNF and MINT25 were most sensitive molecular markers of early stage gastric cancer, whereas PRDM5 and MLF1 were markers of a field defect. There was a close correlation (r = 0.5-0.9, P = .03-.001) between methylation levels in tumor biopsy and gastric washes. MINT25 methylation had the best sensitivity (90%), specificity (96%), and area under the receiver operating characteristic curve (0.961) in terms of tumor detection in gastric washes. Conclusions: These findings suggest MINT25 is a sensitive and specific marker for screening in gastric cancer. Additionally, we have developed a new method for gastric cancer detection by DNA methylation in gastric washes.

UR - http://www.scopus.com/inward/record.url?scp=66149149772&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=66149149772&partnerID=8YFLogxK

U2 - 10.1053/j.gastro.2009.02.085

DO - 10.1053/j.gastro.2009.02.085

M3 - Article

VL - 136

SP - 2149

EP - 2158

JO - Gastroenterology

JF - Gastroenterology

SN - 0016-5085

IS - 7

ER -