<P><B>Background and Purpose</B></P><P>The pathogenesis of moyamoya disease (MMD) remains poorly understood, and no reliable molecular biomarkers for MMD have been identified to date. The present study aimed to identify e...
http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
https://www.riss.kr/link?id=A107419372
2018
-
SCIE,SCOPUS,KCI등재
학술저널
350-361(12쪽)
0
상세조회0
다운로드다국어 초록 (Multilingual Abstract)
<P><B>Background and Purpose</B></P><P>The pathogenesis of moyamoya disease (MMD) remains poorly understood, and no reliable molecular biomarkers for MMD have been identified to date. The present study aimed to identify e...
<P><B>Background and Purpose</B></P><P>The pathogenesis of moyamoya disease (MMD) remains poorly understood, and no reliable molecular biomarkers for MMD have been identified to date. The present study aimed to identify epigenetic biomarkers for use in the diagnosis of MMD. </P><P><B>Methods</B></P><P>We performed integrated analyses of gene expression profiles and DNA methylation profiles in endothelial colony forming cells (ECFCs) from three patients with MMD and two healthy individuals. Candidate gene mRNA expression and DNA methylation status were further validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and pyrosequencing analysis of an expanded ECFC sample set from nine patients with MMD and ten controls. We evaluated the diagnostic accuracy of the potential biomarkers identified here using receiver operating characteristic curve analyses and further measured major angiogenic factor expression levels using a tube formation assay and RT-qPCR. </P><P><B>Results</B></P><P>Five candidate genes were selected via integrated analysis; all five were upregulated by hypomethylation of specific promoter CpG sites. After further validation in an expanded sample set, we identified a candidate biomarker gene, sortilin 1 (<I>SORT1</I>). DNA methylation status at a specific <I>SORT1</I> promoter CpG site in ECFCs readily distinguished patients with MMD from the normal controls with high accuracy (area under the curve 0.98, sensitivity 83.33%, specificity 100%). Furthermore, <I>SORT1</I> overexpression suppressed endothelial cell tube formation and modulated major angiogenic factor and matrix metalloproteinase-9 expression, implying <I>SORT1</I> involvement in MMD pathogenesis. </P><P><B>Conclusions</B></P><P>Our findings suggest that DNA methylation status at the <I>SORT1</I> promoter CpG site may be a potential biomarker for MMD.</P>