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  3. Comparative analysis of patient-derived organoids among oral squamous cell carcinoma and mucosa identifies the distinct features

Comparative analysis of patient-derived organoids among oral squamous cell carcinoma and mucosa identifies the distinct features

  • Arch Oral Biol. 2026 Apr:184:106520. doi: 10.1016/j.archoralbio.2026.106520.
Jianguo Gan 1,  Wanrong Meng 2,  Dan Yang 3,  Xiaodong Feng 4,  Guiquan Zhu 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, China; State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
  • 2 State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
  • 3 State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
  • 4 State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, China. Electronic address: [email protected].
  • 5 State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, China. Electronic address: [email protected].
PMID: 41564798 DOI: 10.1016/j.archoralbio.2026.106520
Abstract

Objective: This study aimed to establish matched patient-derived organoids from oral squamous cell carcinoma (PDO-T) and adjacent normal mucosa (PDO-N), characterize their distinct features, and evaluate their impact on drug response.

Design: PDOs were generated from primary OSCC tissues and matched adjacent normal mucosa obtained from 18 patients. Morphological and histological characteristics were assessed using brightfield microscopy and phalloidin staining. Immunohistochemistry was performed to evaluate differential marker expression. Drug response assays were conducted in paired PDO-T and PDO-N to assess chemotherapeutic sensitivity.

Results: We successfully established 5 PDO-T and 15 PDO-N lines, with PDO-N exhibiting a higher success rate (∼80 %). Morphological analysis showed that PDO-N formed spherical structures with a central cavity and polarity, while PDO-T displayed irregular structures with heterogeneous cell arrangements. Immunohistochemistry revealed broad distribution of Ki-67, p63 and YAP/TAZ in PDO-T, contrasting with their basal layer restriction in PDO-N. p53 was strongly positive in PDO-T. CK5 and CK13 exhibited a stratified pattern in PDO-N. Importantly, drug testing in paired PDO-T and PDO-N revealed divergent responses, with PDO-N generally more resistant and able to maintain morphological integrity under high-dose treatment.

Conclusion: Our comparative analysis delineates distinct features between PDO-T and PDO-N in morphology, biomarker expression, and drug response. These findings provide an intuitive framework for their identification, thereby improving the accuracy of drug screening and enhancing the translational value of PDOs.

Keywords

Carcinogenesis; Oral mucosa; Oral squamous cell carcinoma; Patient-derived organoids; Therapeutic accuracy.

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