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Genomic and single-cell characterization of patient-derived tumor organoid models of head and neck squamous cell carcinoma.
Um, Jung Hyun; Zheng, Yueyuan; Mao, Qiong; Nam, Chehyun; Zhao, Hua; Koh, Yoon Woo; Shin, Su-Jin; Park, Young Min; Lin, De-Chen.
Afiliación
  • Um JH; Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Korea.
  • Zheng Y; Clinical Big Data Research Center, Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen 518107, P.R. China.
  • Mao Q; Clinical Big Data Research Center, Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen 518107, P.R. China.
  • Nam C; Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, Guangzhou Medical University, Guangzhou, 510120, P.R. China.
  • Zhao H; Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, USA.
  • Koh YW; Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, USA.
  • Shin SJ; Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Korea.
  • Park YM; Department of Pathology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
  • Lin DC; Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Korea.
bioRxiv ; 2024 Jul 02.
Article en En | MEDLINE | ID: mdl-39005427
ABSTRACT
Head and Neck Squamous Cell Carcinoma (HNSCC) remains a significant health burden due to tumor heterogeneity and treatment resistance, emphasizing the need for improved biological understanding and tailored therapies. This study enrolled 31 HNSCC patients for the establishment of patient-derived tumor organoids (PDOs), which faithfully maintained genomic features and histopathological traits of primary tumors. Long-term culture preserved key characteristics, affirming PDOs as robust representative models. PDOs demonstrated predictive capability for cisplatin treatment responses, correlating ex vivo drug sensitivity with patient outcomes. Bulk and single-cell RNA sequencing unveiled molecular subtypes and intratumor heterogeneity (ITH) in PDOs, paralleling patient tumors. Notably, a hybrid epithelial-mesenchymal transition (hEMT)-like ITH program is associated with cisplatin resistance and poor patient survival. Functional analyses identified amphiregulin (AREG) as a potential regulator of the hybrid epithelial/mesenchymal state. Moreover, AREG contributes to cisplatin resistance via EGFR pathway activation, corroborated by clinical samples. In summary, HNSCC PDOs serve as reliable and versatile models, offer predictive insights into ITH programs and treatment responses, and uncover potential therapeutic targets for personalized medicine.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos