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; Mee Yon Cho; Lanlan Shen; Jaroslav Jelinek; Jean Pierre J. Issa

doi:10.1053/j.gastro.2009.02.085

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, Mee Yon Cho, Lanlan Shen, Jaroslav Jelinek, Jean Pierre J. Issa

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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 language	English
Pages (from-to)	2149-2158
Number of pages	10
Journal	Gastroenterology
Volume	136
Issue number	7
DOIs	https://doi.org/10.1053/j.gastro.2009.02.085
Publication status	Published - 2009 Jun

Bibliographical note

Funding Information:
Funding This work was supported in part by the National Institutes of Health grants CA098006 and CA105346. J.–P.J.I. is an American Cancer Society Clinical Research Professor supported by a generous gift from the F.M. Kirby Foundation. H.–S.K. was supported by grant 2006-070-C00031 from the Korea Research Foundation and an intramural grant-in-aid from Yonsei University Wonju College of Medicine (2006). DNA sequencing in the Core Sequencing facility at the M.D. Anderson Cancer Center is supported by Core Grant CA16672 from the National Institutes of Health.

All Science Journal Classification (ASJC) codes

Hepatology
Gastroenterology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1053/j.gastro.2009.02.085

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Watanabe, Y., Kim, H. S., Castoro, R. J., Chung, W., Estecio, M. R. H., Kondo, K., Guo, Y., Ahmed, S. S., Toyota, M., Itoh, F., Suk, K. T., Cho, M. Y., Shen, L., Jelinek, J., & 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

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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 Cho, {Mee Yon} and Lanlan Shen and Jaroslav Jelinek and Issa, {Jean Pierre J.}",

note = "Funding Information: Funding This work was supported in part by the National Institutes of Health grants CA098006 and CA105346. J.–P.J.I. is an American Cancer Society Clinical Research Professor supported by a generous gift from the F.M. Kirby Foundation. H.–S.K. was supported by grant 2006-070-C00031 from the Korea Research Foundation and an intramural grant-in-aid from Yonsei University Wonju College of Medicine (2006). DNA sequencing in the Core Sequencing facility at the M.D. Anderson Cancer Center is supported by Core Grant CA16672 from the National Institutes of Health. ",

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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, Mee Yon

AU - Shen, Lanlan

AU - Jelinek, Jaroslav

AU - Issa, Jean Pierre J.

N1 - Funding Information: Funding This work was supported in part by the National Institutes of Health grants CA098006 and CA105346. J.–P.J.I. is an American Cancer Society Clinical Research Professor supported by a generous gift from the F.M. Kirby Foundation. H.–S.K. was supported by grant 2006-070-C00031 from the Korea Research Foundation and an intramural grant-in-aid from Yonsei University Wonju College of Medicine (2006). DNA sequencing in the Core Sequencing facility at the M.D. Anderson Cancer Center is supported by Core Grant CA16672 from the National Institutes of Health.

PY - 2009/6

Y1 - 2009/6

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.

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

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

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