2. Academic Validation
  3. Organoid morphology-guided classification for oral cancer reveals prognosis

Organoid morphology-guided classification for oral cancer reveals prognosis

  • Cell Rep Med. 2025 May 20;6(5):102129. doi: 10.1016/j.xcrm.2025.102129.
Mi Rim Lee 1,  Sumin Kang 1,  Jonghyun Lee 2,  Sun-Young Kong 3,  Youngwook Kim 4,  Yu-Sun Lee 5,  Hye Won Shon 5,  Gyeongmin Kang 1,  Jiyoung Lee 5,  Suk Min Youn 6,  Da Woon Kwack 6,  Joo Yong Park 6,  Soung Min Kim 7,  Wonyoung Choi 8,  Jong-Ho Lee 9,  Dongkwan Shin 10,  Ik-Jae Kwon 11,  Sung-Woen Choi 12,  Yun-Hee Kim 13
Affiliations

Affiliations

  • 1 Molecular Imaging Branch, Division of Convergence Technology, Research Institute of National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi-do 10408, Republic of Korea; Department 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.
  • 2 Bioinformatics Branch, Division of Cancer Data Science, Research Institute of National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi-do 10408, Republic of Korea.
  • 3 Department 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; Targeted 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; Department of Laboratory Medicine, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi-do 10408, Republic of Korea.
  • 4 Department 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.
  • 5 Molecular Imaging Branch, Division of Convergence Technology, Research Institute of National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi-do 10408, Republic of Korea.
  • 6 Oral Oncology Clinic, Research Institute and Hospital, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi-do 10408, Republic of Korea.
  • 7 Department 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.
  • 8 Department 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; Center for Clinical Trials, Research Institute and Hospital, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi-do 10408, Republic of Korea; Cancer 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.
  • 9 Oral Oncology Clinic, Research Institute and Hospital, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi-do 10408, Republic of Korea; Department 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.
  • 10 Department 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; Bioinformatics Branch, Division of Cancer Data Science, Research Institute of National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi-do 10408, Republic of Korea. Electronic address: dshin@ncc.re.kr.
  • 11 Department 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. Electronic address: ijkwon@snu.ac.kr.
  • 12 Department 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; Oral Oncology Clinic, Research Institute and Hospital, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi-do 10408, Republic of Korea; Rare & 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. Electronic address: choiomfs@ncc.re.kr.
  • 13 Molecular Imaging Branch, Division of Convergence Technology, Research Institute of National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi-do 10408, Republic of Korea; Department 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. Electronic address: sensia37@ncc.re.kr.
PMID: 40359934 DOI: 10.1016/j.xcrm.2025.102129
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.

Keywords

combination therapy; morphology analysis; oral cancer; organoids.

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