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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Exploring the DNA methylome of Korean patients with colorectal cancer consolidates the clinical implications of cancer-associated methylation markers

  • Sejoon Lee (Precision Medicine Center, Seoul National University Bundang Hospital) ;
  • Kil-yong Lee (Department of Surgery, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Ji-Hwan Park (Korea Bioinformation Center (KOBIC), Korea Research Institute of Bioscience and Biotechnology) ;
  • Duck-Woo Kim (Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine) ;
  • Heung-Kwon Oh (Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine) ;
  • Seong-Taek Oh (Department of Surgery, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Jongbum Jeon (Korea Bioinformation Center (KOBIC), Korea Research Institute of Bioscience and Biotechnology) ;
  • Dongyoon Lee (Korea Bioinformation Center (KOBIC), Korea Research Institute of Bioscience and Biotechnology) ;
  • Soobok Joe (Korea Bioinformation Center (KOBIC), Korea Research Institute of Bioscience and Biotechnology) ;
  • Hoang Bao Khanh Chu (Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University) ;
  • Jisun Kang (Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University) ;
  • Jin-Young Lee (Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University) ;
  • Sheehyun Cho (Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University) ;
  • Hyeran Shim (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) ;
  • Jin Ok Yang (Korea Bioinformation Center (KOBIC), Korea Research Institute of Bioscience and Biotechnology) ;
  • Jaeim Lee (Department of Surgery, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Sung-Bum Kang (Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine)
  • Received : 2023.06.19
  • Accepted : 2023.11.13
  • Published : 2024.03.31
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Abstract

Aberrant DNA methylation plays a critical role in the development and progression of colorectal cancer (CRC), which has high incidence and mortality rates in Korea. Various CRC-associated methylation markers for cancer diagnosis and prognosis have been developed; however, they have not been validated for Korean patients owing to the lack of comprehensive clinical and methylome data. Here, we obtained reliable methylation profiles for 228 tumor, 103 adjacent normal, and two unmatched normal colon tissues from Korean patients with CRC using an Illumina Infinium EPIC array; the data were corrected for biological and experiment biases. A comparative methylome analysis confirmed the previous findings that hypermethylated positions in the tumor were highly enriched in CpG island and promoter, 5' untranslated, and first exon regions. However, hypomethylated positions were enriched in the open-sea regions considerably distant from CpG islands. After applying a CpG island methylator phenotype (CIMP) to the methylome data of tumor samples to stratify the CRC patients, we consolidated the previously established clinicopathological findings that the tumors with high CIMP signatures were significantly enriched in the right colon. The results showed a higher prevalence of microsatellite instability status and MLH1 methylation in tumors with high CMP signatures than in those with low or non-CIMP signatures. Therefore, our methylome analysis and dataset provide insights into applying CRC-associated methylation markers for Korean patients regarding cancer diagnosis and prognosis.

Keywords

Acknowledgement

This research was supported by the Bio & Medical Technology Development Program (grant number: NRF-2017M3A9A7050614, NRF-2017M3A9A7050610 and NRF-2023M3A9A7009442) and the Korea BioData Station Program.

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