<P><B>Background</B></P><P>Colorectal cancer (CRC) screening is the most efficient strategy to reduce disease-related mortality. Frequent aberrant DNA methylation is known to occur in selected genes and early during CRC d...
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https://www.riss.kr/link?id=A107507901
2017
-
SCOPUS,SCIE
학술저널
126
0
상세조회0
다운로드다국어 초록 (Multilingual Abstract)
<P><B>Background</B></P><P>Colorectal cancer (CRC) screening is the most efficient strategy to reduce disease-related mortality. Frequent aberrant DNA methylation is known to occur in selected genes and early during CRC d...
<P><B>Background</B></P><P>Colorectal cancer (CRC) screening is the most efficient strategy to reduce disease-related mortality. Frequent aberrant DNA methylation is known to occur in selected genes and early during CRC development, which has emerged as a new epigenetic biomarker for early detection of CRC. Previously, we reported that we identified that CpG sites of <I>SDC2</I> were aberrantly methylated in tumor tissues of most CRC patients through comprehensive methylation analysis and demonstrated a high potential of quantification of <I>SDC2</I> methylation in blood for early detection of colorectal cancer. In this study, we aim to investigate the feasibility of quantifying <I>SDC2</I> methylation in stool DNA for the early detection of CRC. The objective of this study was to confirm a high frequency of <I>SDC2</I> methylation in tumor tissues at various stages of CRC and investigate the feasibility of a quantitative test for <I>SDC2</I> methylation in fecal DNA by highly sensitive and accurate real-time PCR for early detection of CRC.</P><P><B>Methods</B></P><P>Bisulfite-pyrosequencing assay was performed to measure the <I>SDC2</I> methylation status in tissue samples. For methylation analysis in stool DNA, a highly sensitive and accurate method was applied which implements consecutive two rounds of PCR consisting of unidirectional linear target enrichment (LTE) of <I>SDC2</I> and quantitative methylation-specific real time PCR (qMSP) for <I>SDC2</I>, named as me<I>SDC2</I> LTE-qMSP assay. Its limit of detection was 0.1% methylation (corresponding to ~ 6 copies in total ~ 6200 genome copies).</P><P><B>Results</B></P><P>Positive <I>SDC2</I> methylation was observed in 100% of primary tumors, 90.6% of adenomatous polyps, 94.1% of hyperplastic polyps, and 0% of normal tissues. <I>SDC2</I> methylation level also significantly (<I>P</I> < 0.01) increased according to the severity of lesions. In stool DNA test for <I>SDC2</I> methylation by LTE-qMSP comparing CRC patients with various stages (I to IV) (<I>n</I> = 50) and precancerous lesions (<I>n</I> = 21) with healthy subjects (<I>n</I> = 22), the overall sensitivity was 90.0% for detecting CRC and 33.3% for detecting small polyps, with a specificity of 90.9%.</P><P><B>Conclusions</B></P><P>Taken together, our result indicates that stool DNA-based <I>SDC2</I> methylation test by LTE-qMSP is a potential noninvasive diagnostic tool for early detection of CRC.</P>
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