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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)
  • Received : 2017.01.31
  • Accepted : 2017.04.24
  • Published : 2017.05.31

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.

Acknowledgement

Supported by : Korean Health Industry Development Institute (KHIDI), National Research Foundation of Korea (NRF)

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