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Blood Free-Circulating DNA Testing of Methylated RUNX3 Is Useful for Diagnosing Early Gastric Cancer

The main modalities for gastric cancer screening are limited to upper gastrointestinal endoscopy and contrast radiography. The former is invasive, and the latter has high false-negative rates. Thus, alternative diagnostic strategies are required. One solution may be a liquid biopsy. Methylated RUNX3...

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Autores principales: Hideura, Eizaburou, Suehiro, Yutaka, Nishikawa, Jun, Shuto, Takuya, Fujimura, Hiroyuki, Ito, Shunsuke, Goto, Atsushi, Hamabe, Kouichi, Saeki, Issei, Okamoto, Takeshi, Higaki, Shingo, Fujii, Ikuei, Suzuki, Chieko, Hoshida, Tomomi, Matsumoto, Toshihiko, Takami, Taro, Sakaida, Isao, Yamasaki, Takahiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226141/
https://www.ncbi.nlm.nih.gov/pubmed/32224873
http://dx.doi.org/10.3390/cancers12040789
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author Hideura, Eizaburou
Suehiro, Yutaka
Nishikawa, Jun
Shuto, Takuya
Fujimura, Hiroyuki
Ito, Shunsuke
Goto, Atsushi
Hamabe, Kouichi
Saeki, Issei
Okamoto, Takeshi
Higaki, Shingo
Fujii, Ikuei
Suzuki, Chieko
Hoshida, Tomomi
Matsumoto, Toshihiko
Takami, Taro
Sakaida, Isao
Yamasaki, Takahiro
author_facet Hideura, Eizaburou
Suehiro, Yutaka
Nishikawa, Jun
Shuto, Takuya
Fujimura, Hiroyuki
Ito, Shunsuke
Goto, Atsushi
Hamabe, Kouichi
Saeki, Issei
Okamoto, Takeshi
Higaki, Shingo
Fujii, Ikuei
Suzuki, Chieko
Hoshida, Tomomi
Matsumoto, Toshihiko
Takami, Taro
Sakaida, Isao
Yamasaki, Takahiro
author_sort Hideura, Eizaburou
collection PubMed
description The main modalities for gastric cancer screening are limited to upper gastrointestinal endoscopy and contrast radiography. The former is invasive, and the latter has high false-negative rates. Thus, alternative diagnostic strategies are required. One solution may be a liquid biopsy. Methylated RUNX3 is a well-known biomarker of gastric cancer but it is very difficult to detect with conventional bisulfite-based methylation assays when only a small amount of serum is available. We developed the combined restriction digital PCR (CORD) assay, a new methylation assay allowing for the counting of as little as one copy of a methylated gene in a small sample of DNA without necessitating DNA bisulfite treatment. We evaluated the sensitivity and specificity of the serum DNA testing of methylated RUNX3 by the CORD assay for the detection of early gastric cancer using 50 patients with early gastric cancer and 61 control individuals. The CORD assay had a sensitivity of 50.0% and a specificity of 80.3% for early gastric cancer. Methylated RUNX3 copies were significantly associated with tumor size, massive submucosal invasion, and lymph-vascular invasion. After the treatment, the median number of methylated RUNX3 copies was significantly decreased. The CORD assay may provide an alternative screening strategy to detect even early-stage gastric cancer.
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spelling pubmed-72261412020-05-18 Blood Free-Circulating DNA Testing of Methylated RUNX3 Is Useful for Diagnosing Early Gastric Cancer Hideura, Eizaburou Suehiro, Yutaka Nishikawa, Jun Shuto, Takuya Fujimura, Hiroyuki Ito, Shunsuke Goto, Atsushi Hamabe, Kouichi Saeki, Issei Okamoto, Takeshi Higaki, Shingo Fujii, Ikuei Suzuki, Chieko Hoshida, Tomomi Matsumoto, Toshihiko Takami, Taro Sakaida, Isao Yamasaki, Takahiro Cancers (Basel) Article The main modalities for gastric cancer screening are limited to upper gastrointestinal endoscopy and contrast radiography. The former is invasive, and the latter has high false-negative rates. Thus, alternative diagnostic strategies are required. One solution may be a liquid biopsy. Methylated RUNX3 is a well-known biomarker of gastric cancer but it is very difficult to detect with conventional bisulfite-based methylation assays when only a small amount of serum is available. We developed the combined restriction digital PCR (CORD) assay, a new methylation assay allowing for the counting of as little as one copy of a methylated gene in a small sample of DNA without necessitating DNA bisulfite treatment. We evaluated the sensitivity and specificity of the serum DNA testing of methylated RUNX3 by the CORD assay for the detection of early gastric cancer using 50 patients with early gastric cancer and 61 control individuals. The CORD assay had a sensitivity of 50.0% and a specificity of 80.3% for early gastric cancer. Methylated RUNX3 copies were significantly associated with tumor size, massive submucosal invasion, and lymph-vascular invasion. After the treatment, the median number of methylated RUNX3 copies was significantly decreased. The CORD assay may provide an alternative screening strategy to detect even early-stage gastric cancer. MDPI 2020-03-26 /pmc/articles/PMC7226141/ /pubmed/32224873 http://dx.doi.org/10.3390/cancers12040789 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hideura, Eizaburou
Suehiro, Yutaka
Nishikawa, Jun
Shuto, Takuya
Fujimura, Hiroyuki
Ito, Shunsuke
Goto, Atsushi
Hamabe, Kouichi
Saeki, Issei
Okamoto, Takeshi
Higaki, Shingo
Fujii, Ikuei
Suzuki, Chieko
Hoshida, Tomomi
Matsumoto, Toshihiko
Takami, Taro
Sakaida, Isao
Yamasaki, Takahiro
Blood Free-Circulating DNA Testing of Methylated RUNX3 Is Useful for Diagnosing Early Gastric Cancer
title Blood Free-Circulating DNA Testing of Methylated RUNX3 Is Useful for Diagnosing Early Gastric Cancer
title_full Blood Free-Circulating DNA Testing of Methylated RUNX3 Is Useful for Diagnosing Early Gastric Cancer
title_fullStr Blood Free-Circulating DNA Testing of Methylated RUNX3 Is Useful for Diagnosing Early Gastric Cancer
title_full_unstemmed Blood Free-Circulating DNA Testing of Methylated RUNX3 Is Useful for Diagnosing Early Gastric Cancer
title_short Blood Free-Circulating DNA Testing of Methylated RUNX3 Is Useful for Diagnosing Early Gastric Cancer
title_sort blood free-circulating dna testing of methylated runx3 is useful for diagnosing early gastric cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226141/
https://www.ncbi.nlm.nih.gov/pubmed/32224873
http://dx.doi.org/10.3390/cancers12040789
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