Usefulness of plasma epigenetic changes of five major genes involved in the pathogenesis of colorectal cancer |
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Authors: | 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 |
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Institution: | 1. Department of Internal Medicine, Seonam University Namgwang Hospital, Gwang-ju, South Korea 5. Brain Korea 21 Project, Center for Biomedical Human Resources, Chonnam National University, Gwangju, South Korea 2. Department of Colon and Rectal Surgery, Chonnam National University Hwasun Hospital, Hwasun, South Korea 4. Department of Laboratory Medicine and Mitochondrial Research Laboratory, Chonnam National University Hwasun Hospital, Hwasun, South Korea 3. Department of Internal Medicine, Kwangju Christian Hospital, Gwang-ju, South Korea 6. Department of Preventive Medicine, the Armed Forces Command, Seoul, South Korea 7. Department of Laboratory Medicine, 160 Ilsim-ri, Hwasun-eup, Hwasun-gun, Jeollanam-do, 519-809, South Korea
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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 (OR?=?6.67, 95 % CI?=?1.19–23.4, P?=?0.045) 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 this study, E-cad and APC genes may be particularly useful epigenetic biomarkers in plasma for the detection of CRC. Additionally, APC may able to identify early potential CRC. |
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