Differential LINE-1 Hypomethylation of Gastric Low-Grade Dysplasia from High Grade Dysplasia and Intramucosal Cancer |
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Authors: | Lee Jeong Rok Chung Woo Chul Kim Jin Dong Lee Kang Moon Paik Chang Nyol Jung Sung Hoon Jung Ji Han Lee Yun Kyung Han Sok Won |
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Institution: | Department of Internal Medicine, Cheju Halla General Hospital, Jeju, Korea. |
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Abstract: | Background/AimsGastric epithelial dysplasia is considered a precancerous lesion with a variable clinical course. There is disagreement, however, regarding histology-based diagnoses, which has led to confusion in choosing a therapeutic plan. New objective markers are needed to determine which lesions progress to true malignancy. We measured LINE-1 methylation levels, which have been reported to strongly correlate with the global methylation level in gastric epithelial dysplasia and intramucosal cancer.MethodsA total of 145 tissue samples were analyzed by two histopathologists. All tissues were excised by therapeutic endoscopic mucosal resection and paired with adjacent normal tissue samples. A modified long interspersed nucleotide elements-combined bisulfite restriction analysis (COBRA-LINE-1) method was used.ResultsGastric epithelial dysplasia and intramucosal cancer tissues had significantly lower levels of LINE-1 methylation than adjacent normal gastric tissues. High-grade dysplasia and intramucosal cancer were distinguishable from low-grade dysplasia based on LINE-1 methylation levels. Furthermore, the distinction could be determined with high sensitivity and specificity, as shown by the receiver operating characteristic (ROC) curve (AUC, 0.82; 95% confidence interval, 0.74 to 0.88).ConclusionsLINE-1 methylation levels may provide a diagnostic tool for identifying high-grade dysplasia and intramucosal cancer. |
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Keywords: | LINE-1 methylation Gastric epithelial dysplasia Intramucosal cancer |
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