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서울대학교

Cell Rep. Med., May 12, 2025 | https://doi.org/10.1016/j.xcrm.2025.102129 Organoid morphology-guided classification for oral cancer reveals prognosis

Mi Rim Lee,^1,2,11 Sumin Kang,^1,2,11 Jonghyun Lee,^3,11 Sun-Young Kong,^2,4,5 Youngwook Kim,² Yu-Sun Lee,¹ Hye Won Shon,¹ Gyeongmin Kang,^1,2 Jiyoung Lee,¹ Suk Min Youn,⁶ Da Woon Kwack,⁶Joo Yong Park,⁶ Soung Min Kim,⁷ Wonyoung Choi,^2,8,9 Jong-Ho Lee,^6,7 Dongkwan Shin,^2,3,12,* Ik-Jae Kwon,^7,12,* Sung-Woen Choi,^2,6,10,12,*and Yun-Hee Kim ^1,2,12,13,*

¹Molecular Imaging Branch, Division of Convergence Technology, Research Institute of National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi-do 10408, Republic of Korea
²Department of Cancer Biomedical Science, National Cancer Center Graduate School of Cancer Science and Policy, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi-do 10408, Republic of Korea
³Bioinformatics Branch, Division of Cancer Data Science, Research Institute of National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi-do 10408, Republic of Korea
⁴Targeted Therapy Branch, Division of Rare and Refractory Cancer, Research Institute of National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi-do 10408, Republic of Korea
⁵Department of Laboratory Medicine, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi-do 10408, Republic of Korea
⁶Oral Oncology Clinic, Research Institute and Hospital, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi-do 10408, Republic of Korea
⁷Department of Oral and Maxillofacial Surgery, Seoul National University Dental Hospital, Dental Research Institute, School of Dentistry, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea
⁸Center for Clinical Trials, Research Institute and Hospital, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi-do 10408, Republic of Korea
⁹Cancer Molecular Biology Branch, Division of Cancer Biology, Research Institute of National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi-do 10408, Republic of Korea
¹⁰Rare & Pediatric Cancer Branch, Division of Rare and Refractory Cancer, Research Institute of National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi-do 10408, Republic of Korea
¹¹These authors contributed equally
¹²These authors contributed equally
¹³Lead contact

^*Corresponding authors: correspondence to Dongkwan Shin, Ik-Jae Kwon, Sung-Woen Choi or Yun-Hee Kim

Abstract

Oral cancer is an aggressive malignancy with a survival rate below 50% in advanced stages due to low mutation rates, lack of molecular subtypes, and limited treatment targets. This study presents a pioneering approach to classifying oral cancer subtypes based on the morphology of patient-derived organoids (PDOs) and proposes a therapeutic strategy. We establish 76 cancer and 81 normal PDOs. For cancer PDOs, both manual classification and AI-based scoring are utilized to categorize them into three distinct subtypes: normal-like, dense, and grape-like. These subtypes correlate with unique transcriptomic profiles, genetic mutations, and clinical outcomes, with patients harboring dense and grape-like organoids exhibiting poorer prognoses. Furthermore, drug response assessments of 14 single agents and cisplatin combination therapies identify a synergistic treatment approach for resistant subtypes. This study highlights the potential of integrating morphology-based classification with genomic and transcriptomic analyses to refine oral cancer subtyping and develop effective treatment strategies.

논문정보

형식Research article
게재일2025년 05월 (BRIC 등록일 2025-05-14)
연구진국내 연구진
분야 생명과학 > 노화/암생물학

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