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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Deciphering the DNA methylation landscape of colorectal cancer in a Korean cohort

  • Seok-Byung Lim (Division of Colon and Rectal Surgery, Department of Surgery, Asan Medical Center, College of Medicine, Ulsan University) ;
  • Soobok Joe (Korea Bioinformation Center (KOBIC), Korea Research Institute of Bioscience and Biotechnology) ;
  • Hyo-Ju Kim (Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University) ;
  • Jong Lyul Lee (Division of Colon and Rectal Surgery, Department of Surgery, Asan Medical Center, College of Medicine, Ulsan University) ;
  • In Ja Park (Division of Colon and Rectal Surgery, Department of Surgery, Asan Medical Center, College of Medicine, Ulsan University) ;
  • Yong Sik Yoon (Division of Colon and Rectal Surgery, Department of Surgery, Asan Medical Center, College of Medicine, Ulsan University) ;
  • Chan Wook Kim (Division of Colon and Rectal Surgery, Department of Surgery, Asan Medical Center, College of Medicine, Ulsan University) ;
  • Jong-Hwan Kim (Korea Bioinformation Center (KOBIC), Korea Research Institute of Bioscience and Biotechnology) ;
  • Sangok Kim (Korea Bioinformation Center (KOBIC), Korea Research Institute of Bioscience and Biotechnology) ;
  • Jin-Young Lee (Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University) ;
  • Hyeran Shim (Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University) ;
  • Hoang Bao Khanh Chu (Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University) ;
  • Sheehyun Cho (Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University) ;
  • Jisun Kang (Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University) ;
  • Si-Cho Kim (Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University) ;
  • Hong Seok Lee (Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University) ;
  • Young-Joon Kim (Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University) ;
  • Seon-Young Kim (Korea Bioinformation Center (KOBIC), Korea Research Institute of Bioscience and Biotechnology) ;
  • Chang Sik Yu (Division of Colon and Rectal Surgery, Department of Surgery, Asan Medical Center, College of Medicine, Ulsan University)
  • Received : 2023.06.20
  • Accepted : 2023.08.19
  • Published : 2023.10.31
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Abstract

Aberrant DNA methylation plays a pivotal role in the onset and progression of colorectal cancer (CRC), a disease with high incidence and mortality rates in Korea. Several CRC-associated diagnostic and prognostic methylation markers have been identified; however, due to a lack of comprehensive clinical and methylome data, these markers have not been validated in the Korean population. Therefore, in this study, we aimed to obtain the CRC methylation profile using 172 tumors and 128 adjacent normal colon tissues of Korean patients with CRC. Based on the comparative methylome analysis, we found that hypermethylated positions in the tumor were predominantly concentrated in CpG islands and promoter regions, whereas hypomethylated positions were largely found in the open-sea region, notably distant from the CpG islands. In addition, we stratified patients by applying the CpG island methylator phenotype (CIMP) to the tumor methylome data. This stratification validated previous clinicopathological implications, as tumors with high CIMP signatures were significantly correlated with the proximal colon, higher prevalence of microsatellite instability status, and MLH1 promoter methylation. In conclusion, our extensive methylome analysis and the accompanying dataset offers valuable insights into the utilization of CRC-associated methylation markers in Korean patients, potentially improving CRC diagnosis and prognosis. Furthermore, this study serves as a solid foundation for further investigations into personalized and ethnicity-specific CRC treatments.

Keywords

Acknowledgement

This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science & ICT (grant number: NRF-2017M3A9A7050614). It was additionally supported by a grant from the National Research Foundation of Korea (NRF-2020M3A9I6A01036057).

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