Comparative detection of aberrantly methylated DNA in preoperative and postoperative stool from patients with colorectal cancers

Yasunobu Nishioka, Takashi Ueki, Koji Hokazono, Kinuko Nagayoshi, Masao Tanaka

研究成果: ジャーナルへの寄稿記事

4 引用 (Scopus)

抄録

Background: Early detection of colorectal cancer (CRC) is crucial to reducing tumor-related mortality. Evaluating aberrantly methylated DNA in stool is promising for CRC screening. However, DNA methylation in the colonic epithelium of background mucosa may compromise stool DNA (sDNA) test results. Thus, we compared aberrant methylation of cancer-related genes in preoperative and postoperative sDNA, with the aim of demonstrating that a cancer-specific methylated allele in sDNA originates from CRCs. Methods: Patients who were to undergo CRC resection in Kyushu University Hospital during 2003-2010 were prospectively enrolled. Preoperative (pre) stool samples from 54 patients, postoperative (post) samples from 52 of the patients and tumor samples were collected. Aberrant promoter methylation of CDH4 and GATA5 was assessed in the primary tumors by methylation-specific polymerase chain reaction (MSP) and in stool samples by real-time MSP. Results: Aberrant methylation of CDH4 and/or GATA5 was detected in 45 of CRC tissue samples (83.3%) and identified in 23 pre sDNA samples (42.3%) from CRC patients. Aberrant methylation was not found in pre sDNA obtained from CRC patients without aberrant methylation of these genes or in post sDNA in any patient. The detection rate of methylated alleles did not correlate with depth of invasion or tumor stage. Conclusion: Our findings demonstrate that aberrantly methylated alleles identified in sDNA originate from CRCs. Although tumor-specific aberrant methylation is found in sDNA from patients harboring early and advanced CRC throughout the colon and rectum, the sensitivity of this test needs to be improved for early detection of CRC.

元の言語英語
ページ(範囲)e81-e87
ジャーナルInternational Journal of Biological Markers
30
発行部数1
DOI
出版物ステータス出版済み - 3 1 2015

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Methylation
Colorectal Neoplasms
DNA
Tumors
Early Detection of Cancer
Neoplasms
Alleles
Genes
Neoplasm Genes
Polymerase chain reaction
DNA Methylation
Rectal Neoplasms
Colonic Neoplasms
Screening
Mucous Membrane
Epithelium
Tissue
Polymerase Chain Reaction
Mortality

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Oncology
  • Clinical Biochemistry
  • Cancer Research

これを引用

Comparative detection of aberrantly methylated DNA in preoperative and postoperative stool from patients with colorectal cancers. / Nishioka, Yasunobu; Ueki, Takashi; Hokazono, Koji; Nagayoshi, Kinuko; Tanaka, Masao.

:: International Journal of Biological Markers, 巻 30, 番号 1, 01.03.2015, p. e81-e87.

研究成果: ジャーナルへの寄稿記事

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title = "Comparative detection of aberrantly methylated DNA in preoperative and postoperative stool from patients with colorectal cancers",
abstract = "Background: Early detection of colorectal cancer (CRC) is crucial to reducing tumor-related mortality. Evaluating aberrantly methylated DNA in stool is promising for CRC screening. However, DNA methylation in the colonic epithelium of background mucosa may compromise stool DNA (sDNA) test results. Thus, we compared aberrant methylation of cancer-related genes in preoperative and postoperative sDNA, with the aim of demonstrating that a cancer-specific methylated allele in sDNA originates from CRCs. Methods: Patients who were to undergo CRC resection in Kyushu University Hospital during 2003-2010 were prospectively enrolled. Preoperative (pre) stool samples from 54 patients, postoperative (post) samples from 52 of the patients and tumor samples were collected. Aberrant promoter methylation of CDH4 and GATA5 was assessed in the primary tumors by methylation-specific polymerase chain reaction (MSP) and in stool samples by real-time MSP. Results: Aberrant methylation of CDH4 and/or GATA5 was detected in 45 of CRC tissue samples (83.3{\%}) and identified in 23 pre sDNA samples (42.3{\%}) from CRC patients. Aberrant methylation was not found in pre sDNA obtained from CRC patients without aberrant methylation of these genes or in post sDNA in any patient. The detection rate of methylated alleles did not correlate with depth of invasion or tumor stage. Conclusion: Our findings demonstrate that aberrantly methylated alleles identified in sDNA originate from CRCs. Although tumor-specific aberrant methylation is found in sDNA from patients harboring early and advanced CRC throughout the colon and rectum, the sensitivity of this test needs to be improved for early detection of CRC.",
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AU - Tanaka, Masao

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N2 - Background: Early detection of colorectal cancer (CRC) is crucial to reducing tumor-related mortality. Evaluating aberrantly methylated DNA in stool is promising for CRC screening. However, DNA methylation in the colonic epithelium of background mucosa may compromise stool DNA (sDNA) test results. Thus, we compared aberrant methylation of cancer-related genes in preoperative and postoperative sDNA, with the aim of demonstrating that a cancer-specific methylated allele in sDNA originates from CRCs. Methods: Patients who were to undergo CRC resection in Kyushu University Hospital during 2003-2010 were prospectively enrolled. Preoperative (pre) stool samples from 54 patients, postoperative (post) samples from 52 of the patients and tumor samples were collected. Aberrant promoter methylation of CDH4 and GATA5 was assessed in the primary tumors by methylation-specific polymerase chain reaction (MSP) and in stool samples by real-time MSP. Results: Aberrant methylation of CDH4 and/or GATA5 was detected in 45 of CRC tissue samples (83.3%) and identified in 23 pre sDNA samples (42.3%) from CRC patients. Aberrant methylation was not found in pre sDNA obtained from CRC patients without aberrant methylation of these genes or in post sDNA in any patient. The detection rate of methylated alleles did not correlate with depth of invasion or tumor stage. Conclusion: Our findings demonstrate that aberrantly methylated alleles identified in sDNA originate from CRCs. Although tumor-specific aberrant methylation is found in sDNA from patients harboring early and advanced CRC throughout the colon and rectum, the sensitivity of this test needs to be improved for early detection of CRC.

AB - Background: Early detection of colorectal cancer (CRC) is crucial to reducing tumor-related mortality. Evaluating aberrantly methylated DNA in stool is promising for CRC screening. However, DNA methylation in the colonic epithelium of background mucosa may compromise stool DNA (sDNA) test results. Thus, we compared aberrant methylation of cancer-related genes in preoperative and postoperative sDNA, with the aim of demonstrating that a cancer-specific methylated allele in sDNA originates from CRCs. Methods: Patients who were to undergo CRC resection in Kyushu University Hospital during 2003-2010 were prospectively enrolled. Preoperative (pre) stool samples from 54 patients, postoperative (post) samples from 52 of the patients and tumor samples were collected. Aberrant promoter methylation of CDH4 and GATA5 was assessed in the primary tumors by methylation-specific polymerase chain reaction (MSP) and in stool samples by real-time MSP. Results: Aberrant methylation of CDH4 and/or GATA5 was detected in 45 of CRC tissue samples (83.3%) and identified in 23 pre sDNA samples (42.3%) from CRC patients. Aberrant methylation was not found in pre sDNA obtained from CRC patients without aberrant methylation of these genes or in post sDNA in any patient. The detection rate of methylated alleles did not correlate with depth of invasion or tumor stage. Conclusion: Our findings demonstrate that aberrantly methylated alleles identified in sDNA originate from CRCs. Although tumor-specific aberrant methylation is found in sDNA from patients harboring early and advanced CRC throughout the colon and rectum, the sensitivity of this test needs to be improved for early detection of CRC.

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