방두희 (연세대학교) | 한빛사논문 > 한빛사

한빛사논문

조회679

연세대학교

CV File 182 kb

Exp. Mol. Med., 01 November 2023 | https://doi.org/10.1038/s12276-023-01119-5 Cancer signature ensemble integrating cfDNA methylation, copy number, and fragmentation facilitates multi-cancer early detection

Su Yeon Kim ^1,15, Seongmun Jeong ^1,15, Wookjae Lee ¹, Yujin Jeon ¹, Yong-Jin Kim ¹, Seowoo Park ¹, Dongin Lee ², Dayoung Go ¹, Sang-Hyun Song ³, Sanghoo Lee ⁴, Hyun Goo Woo ⁵, Jung-Ki Yoon ⁶, Young Sik Park ⁷, Young Tae Kim ^3,8, Se-Hoon Lee ^9,10, Kwang Hyun Kim ¹¹, Yoojoo Lim ¹, Jin-Soo Kim ^1,12, Hwang-Phill Kim ¹, Duhee Bang ^2,* and Tae-You Kim ^1,3,13,14,*

¹IMBdx Inc., Seoul 08506, Republic of Korea.
²Department of Chemistry, Yonsei University, Seoul 03722, Republic of Korea.
³Cancer Research Institute, Seoul National University, Seoul 03080, Republic of Korea.
⁴Seoul Clinical Laboratories Healthcare Inc., Yongin-si, Gyenggi-do 16954, Republic of Korea.
⁵Department of Physiology, Ajou University School of Medicine, Suwon 16499, Republic of Korea.
⁶Division of Pulmonary and Critical Care Medicine, Department of Medicine, Stanford University, Stanford, CA, USA.
⁷Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, Republic of Korea.
⁸Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, Seoul 03080, Republic of Korea.
⁹Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea.
¹⁰Department of Health Sciences and Technology, Samsung Advanced Institute of Health Sciences and Technology, Sungkyunkwan University, Seoul 03063, Republic of Korea.
¹¹Department of Urology, Ewha Womans University Seoul Hospital, Seoul 07804, Republic of Korea.
¹²Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul 07061, Republic of Korea.
¹³Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, Republic of Korea.
¹⁴Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Republic of Korea.
¹⁵These authors contributed equally: Su Yeon Kim, Seongmun Jeong.

^*Corresponding authors: correspondence to Duhee Bang or Tae-You Kim

Abstract

Cell-free DNA (cfDNA) sequencing has demonstrated great potential for early cancer detection. However, most large-scale studies have focused only on either targeted methylation sites or whole-genome sequencing, limiting comprehensive analysis that integrates both epigenetic and genetic signatures. In this study, we present a platform that enables simultaneous analysis of whole-genome methylation, copy number, and fragmentomic patterns of cfDNA in a single assay. Using a total of 950 plasma (361 healthy and 589 cancer) and 240 tissue samples, we demonstrate that a multifeature cancer signature ensemble (CSE) classifier integrating all features outperforms single-feature classifiers. At 95.2% specificity, the cancer detection sensitivity with methylation, copy number, and fragmentomic models was 77.2%, 61.4%, and 60.5%, respectively, but sensitivity was significantly increased to 88.9% with the CSE classifier (p value < 0.0001). For tissue of origin, the CSE classifier enhanced the accuracy beyond the methylation classifier, from 74.3% to 76.4%. Overall, this work proves the utility of a signature ensemble integrating epigenetic and genetic information for accurate cancer detection.

논문정보

형식Research article
게재일2023년 11월 (BRIC 등록일 2023-11-15)
연구진국내(교신)+국외 연구진
분야

댓글 작성 로그인

CV 열람하기

연락처 보기