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Aberrant hypermethylation of OGDHL gene promoter in sporadic colorectal cancer
Affiliation:1. Dept. of Genetics, Animal Biology Group, Faculty of Natural Science, University of Tabriz, Tabriz, Iran;2. Department of Biology, Tabriz Branch of Islamic Azad University, Tabriz, Iran;3. Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran;4. Department of Molecular Medicine, Pasteur Institute of Iran, Tehran, Iran;5. Department of General & Vascular Surgery, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran;1. College of Medicine, Chungbuk National University, Cheongju, Republic of Korea;2. Graduate School of Health Science Business Convergence, Chungbuk National University, Cheongju, Republic of Korea;3. Department of Family Medicine, Samsung Medical Center, Seoul, Republic of Korea;4. Cancer Policy Branch, National Cancer Control Institute, National Cancer Center, Goyang, Republic of Korea;5. Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Republic of Korea;6. Cancer Education Center, Samsung Comprehensive Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea;7. Department of Health Sciences and Technology, Samsung Advanced institute of health Sciences and Technology (SAIHST), Sungkyunkwan University, Seoul, Republic of Korea;8. Department of Health, Behavior, and Society, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland;9. Division of Cancer Policy and Management, National Cancer Control Research Institute, National Cancer Center, Goyang, Republic of Korea;10. Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts;11. Department of Public Health and Preventive Medicine, Chungbuk National University Hospital, Cheongju, Republic of Korea;1. Shandong Center for Disease Control and Prevention, Shandong University Institute of Preventive Medicine, Shandong, China;2. Shandong Blood Center, Shandong, China;1. Department of Medical Oncology, University of Health Sciences, Okmeydani Training and Research Hospital, Istanbul, Turkey;2. Department of Medical Oncology, Yuzuncu Yil University Medical School, Van, Turkey;1. Bezmialem Vakif University, Faculty of Medicine, Department of Medical Oncology, Fatih/Istanbul, Turkey;2. Bezmialem Vakif University, Faculty of Medicine, Department of Internal Medicine, Fatih/Istanbul, Turkey;3. Bezmialem Vakif University, Faculty of Medicine, Department of Biochemistry, Fatih/Istanbul, Turkey;1. Clinical Research Center, The First Affiliated Hospital of Xi''an Jiaotong University, Xi''an, Shaanxi, China;2. School of Nursing and Health, Henan University, Kaifeng, Henan, China;3. Department of Genetics, Northwest Women''s and Children''s Hospital, Xi''an, Shaanxi, China;4. School of Public Health, Xi''an Jiaotong University Health Science Center, Xi''an, Shaanxi, China;5. Center for Evidence-Based Medicine and Clinical Research, Huaihe Hospital of Henan University, Kaifeng, Henan, China;6. Department of General Surgery, Huaihe Hospital of Henan University, Kaifeng, Henan, China
Abstract:
BackgroundAberrant methylation patterns of certain genes including tumor suppressors, a major epigenetic event, contribute mainly to tumorigenesis. Promoter CpG island methylation in Oxoglutarate dehydrogenase like (OGDHL) gene has been reported to reduce gene expression and hence apoptosis induction. This gene has been shown to be involved in colorectal cancer progression. In the present study, we investigated methylation status of OGDHL gene promoter in patients with colorectal cancer and evaluated its potential as a diagnostic biomarker.Methods and materialAfter collecting clinicopathologic data of patients, tumor and matched tumor free margin samples were obtained from 40 individuals; total genomic DNA was extracted and subjected to bisulfite modification. Methylation status of the gene promoter was studied using quantitative methylation-specific PCR method. Finally, its potential as a diagnostic biomarker was evaluated by receiver operating characteristic curve analysis.ResultsThere was not any significant correlation for clinicopathologic features including tumor stage, grade, size, and location with methylation status of OGDHL promoter. However, a significant high methylation level was observed in tumoral tissues compared with nontumoral marginal samples (P < 0.0001). Moreover, receiver operating characteristic curve analysis revealed 97.5% sensitivity and 95%, specificity for OGDHL promoter methylation in a cut off of 27.37% methylation as a biomarker for colorectal cancer.ConclusionThe promoter of OGDHL gene is hypermethylated in colorectal cancer and might be considered as a biomarker for its development.
Keywords:
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