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http://dx.doi.org/10.14348/molcells.2017.0013

Methylation Levels of LINE-1 As a Useful Marker for Venous Invasion in Both FFPE and Frozen Tumor Tissues of Gastric Cancer  

Min, Jimin (Cancer Research Institute, Seoul National University College of Medicine)
Choi, Boram (Department of Life Science, Ewha Womans University)
Han, Tae-Su (Biotherapeutics Translational Research Center, Division of Biomedical Science, Korea Research Institute of Bioscience and Biotechnology)
Lee, Hyuk-Joon (Cancer Research Institute, Seoul National University College of Medicine)
Kong, Seong-Ho (Department of Surgery, Seoul National University College of Medicine)
Suh, Yun-Suhk (Department of Surgery, Seoul National University College of Medicine)
Kim, Tae-Han (Department of Surgery, Seoul National University College of Medicine)
Choe, Hwi-Nyeong (Department of Nursing, Seoul National University Hospital)
Kim, Woo Ho (Department of Pathology, Seoul National University College of Medicine)
Hur, Keun (Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University)
Yang, Han-Kwang (Cancer Research Institute, Seoul National University College of Medicine)
Abstract
Long interspersed nuclear element-1 (LINE-1) is a retrotransposon that contains a CpG island in its 5'-untranslated region. The CpG island of LINE-1 is often heavily methylated in normal somatic cells, which is associated with poor prognosis in various cancers. DNA methylation can differ between formalin-fixed paraffin-embedded (FFPE) and frozen tissues. Therefore, this study aimed to compare the LINE-1 methylation status between the two tissue-storage conditions in gastric cancer (GC) clinical samples and to evaluate whether LINE-1 can be used as an independent prognostic marker for each tissue-storage type. We analyzed four CpG sites of LINE-1 and examined the methylation levels at these sites in 25 FFPE and 41 frozen GC tissues by quantitative bisulfite pyrosequencing. The LINE-1 methylation status was significantly different between the FFPE and frozen GC tissues (p < 0.001). We further analyzed the clinicopathological features in the two groups separately. In the frozen GC tissues, LINE-1 was significantly hypomethylated in GC tissues compared to their corresponding normal gastric mucosa tissues (p < 0.001), and its methylation status was associated with gender, differentiation state, and lymphatic and venous invasion of GC. In the FFPE GC tissues, the methylation levels of LINE-1 differed according to tumor location and venous invasion of GC. In conclusion, LINE-1 can be used as a useful methylation marker for venous invasion in both FFPE and frozen tumor tissues of GC.
Keywords
gastric cancer; LINE-1; pyrosequencing; venous invasion;
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