Usefulness of plasma epigenetic changes of five major genes involved in the pathogenesis of colorectal cancer
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ORIGINAL ARTICLE
Usefulness of plasma epigenetic changes of five major genes involved in the pathogenesis of colorectal cancer Seung-Chul Pack & Hye-Ran Kim & Sang-Woo Lim & Hwan-Young Kim & Jung-Yun Ko & Ki-Sang Lee & David Hwang & Seong-Il Park & Hoon Kang & Sang-Wook Park & Gun-Young Hong & Se-Min Hwang & Myung-Geun Shin & Soong Lee
Accepted: 14 August 2012 / Published online: 19 September 2012 # Springer-Verlag 2012
Abstract Purpose The purpose of present study was to investigate the methylation status of the promoter region in five genes (mothers against decapentaplegic homolog 4, fragile histidine triad protein, death-associated protein kinase 1, adenomatous polyposis coli (APC), and E-cadherin), which are known to be involved in the pathogenesis of colorectal cancer (CRC) and its clinicopathological significance. Methods The study subjects were 60 CRC patients, 40 patients with adenomatous colorectal polyp and 60 healthy control individuals. We further enrolled a total of 16 patients (two patients with Crohn’s disease, two patients with ulcerative colitis, one patient with serrated adenoma, and 11 patients with colorectal cancer). The methylation states of the five genes were determined in peripheral blood plasma
using methylation-specific polymerase chain reaction single-strand conformation polymorphism analysis. Results This study showed the most sensitive epigenetic markers, E-cadherin (60 %), followed by APC (57 %), for detecting CRC. E-cadherin and APC had similar specificities and amplified 84 and 86 %, respectively, of CRC patients compared to non-CRC patients. Additionally, APC was the only marker to be significantly increased (OR0 6.67, 95 % CI01.19–23.4, P00.045) and the most sensitive (57 %) and specific (89 %) marker in stage I CRC. Though we have not examined the paired cancer tissues and plasma, there was relatively high concordant rate (60–80 %) in our limited number of colorectal cancer patients. Conclusions Five genes, promoter methylation, in plasma were statistically significant risk factors in CRC patients. In
Lee S and Kim HR contributed equally to this work. S.-C. Pack : K.-S. Lee : D. Hwang : S.-I. Park : H. Kang : S. Lee (*) Department of Internal Medicine, Seonam University Namgwang Hospital, Gwang-ju, South Korea e-mail: [email protected] S.-W. Lim Department of Colon and Rectal Surgery, Chonnam National University Hwasun Hospital, Hwasun, South Korea
H.-R. Kim Brain Korea 21 Project, Center for Biomedical Human Resources, Chonnam National University, Gwangju, South Korea
S.-M. Hwang Department of Preventive Medicine, the Armed Forces Command, Seoul, South Korea
S.-W. Park : G.-Y. Hong Department of Internal Medicine, Kwangju Christian Hospital, Gwang-ju, South Korea H.-Y. Kim : J.-Y. Ko : M.-G. Shin Department of Laboratory Medicine and Mitochondrial Research Laboratory, Chonnam National University Hwasun Hospital, Hwasun, South Korea
M.-G. Shin (*) Department of Laboratory Medicine, 160 Ilsim-ri, Hwasun-eup, Hwasun-gun, Jeollanam-do 519-809, South Korea e-mail: mgshin@chonn
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