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北京大学学报（医学版） ›› 2025, Vol. 57 ›› Issue (5): 847-851. doi: 10.19723/j.issn.1671-167X.2025.05.006

• 工作综述 • 上一篇    下一篇

口腔鳞癌类器官库的构建及应用

谢尚, 王鹿鸣, 张馨元, 冯秋实, 夏洋洋, 戴姿薇, 单小峰, 蔡志刚*()   

  1. 北京大学口腔医学院·口腔医院口腔颌面外科, 国家口腔医学中心, 国家口腔疾病临床医学研究中心, 口腔生物材料和数字诊疗装备国家工程研究中心, 北京 100081
  • 收稿日期:2025-08-15 出版日期:2025-10-18 发布日期:2025-08-20
  • 通讯作者: 蔡志刚
  • 基金资助:
    国家重点研发计划(2022YFC2504200); 国家自然科学基金(82373434); 国家自然科学基金(82002878)

Construction and application of oral squamous cell carcinoma organoid bank

Shang XIE, Luming WANG, Xinyuan ZHANG, Qiushi FENG, Yangyang XIA, Ziwei DAI, Xiaofeng SHAN, Zhigang CAI*()   

  1. Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, China
  • Received:2025-08-15 Online:2025-10-18 Published:2025-08-20
  • Contact: Zhigang CAI
  • Supported by:
    the National Key Research & Development Program of China(2022YFC2504200); the National Natural Science Foundation of China(82373434); the National Natural Science Foundation of China(82002878)

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摘要： 口腔鳞癌(oral squamous cell carcinoma, OSCC)约占口腔恶性肿瘤的90%以上，全球每年新发病例超过37万例，死亡约18.8万例。我国每年新发病例约6.5万例，死亡约3.5万例，与2015年相比，新发及死亡人数均呈明显上升趋势。尽管口腔鳞癌的治疗方法不断更新，但5年生存率长期停滞于50%~60%，肿瘤异质性及治疗耐药性依然是精准诊疗面临的核心瓶颈。针对OSCC异质性高、治疗耐药的核心瓶颈，我们率先创建OSCC类器官库标准化构建体系(专利名称：一种口腔鳞癌类器官库的构建方法；专利号：ZL202311378598.3)。通过优化培养基组分、精准调控酶消化条件及阶梯式冻存策略，建库成功率提升至>95%，并率先实现同一患者癌组织、淋巴结转移灶及正常黏膜同步培养。基于该类器官库平台，建立高通量药物敏感性检测体系，揭示肿瘤异质性驱动化疗应答差异规律；发现抗唾液酸化癌源性免疫球蛋白(sialylated cancer IgG，SIA-cIgG)通过抑制酪氨酸磷酸酶非受体13(protein tyrosine phosphatase non-receptor 13，PTPN13)介导顺铂原发性/继发性耐药，提出抗SIA-cIgG联合化疗新方案；利用CRISPR编辑类器官模型，阐明WD重复结构蛋白54(WD repeat domain 54, WDR54)通过H3K4me3/H4K16ac表观遗传重编程激活上皮-间充质可塑性(EMP)促转移机制。本平台为OSCC精准治疗提供“全息患者镜像”，被纳入《中华口腔医学会》技术指南(指南名称：人源口腔鳞癌类器官库构建的技术指南；指南编号：CHSA 2024-08)。未来将融合免疫类器官、3D生物打印血管网络及多组学-AI预测系统，推动个体化诊疗临床转化。

关键词: 口腔鳞癌, 类器官库, 精准医疗, 药物筛选, 个体化治疗

Abstract: Oral squamous cell carcinoma (OSCC) accounts for over 90% of oral malignancies, with more than 370 000 new cases and approximately 188 000 deaths annually worldwide. In China, there are roughly 65 000 new cases and 35 000 deaths each year, showing a significant upward trend compared with 2015 statistics. Despite continuous advancements in treatment modalities, the 5-year survival rate remains stagnant at 50%-60%, where tumor heterogeneity and therapy resistance persist as fundamental barriers to precision oncology. To address these critical challenges, this study established a standardized bioban-king protocol for OSCC patient-derived organoids (PDOs) (Patent: Method for constructing an oral squamous cell carcinoma organoid bank, ZL202311378598.3). Through groundbreaking optimization of culture media, enzymatic digestion kinetics, and stepwise cryopreservation, we achieved a biobanking success rate exceeding 95% and pioneered synchronous cultivation of matched primary tumors, lymph node metastases, and adjacent normal mucosa from individual patients, preserving spatial heterogeneity and stromal interactions. Leveraging this platform, we developed high-throughput drug screening: Quantified heterogeneity-driven differential chemoresponse using adenosine triphosphate (ATP)-based viability assays; We discovered resistance mechanisms: Identified sialylated cancer IgG (SIA-cIgG)-mediated cis-platin resistance (primary/secondary) through PTPN13 suppression, with anti-SIA-cIgG combination therapy demonstrating synergistic efficacy. Besides, we elucidated metastatic drivers: CRISPR-Cas9-edited organoids revealed WDR54 promoted metastasis via H3K4me3/H4K16ac epigenetic reprogramming, activating epithelial-mesenchymal plasticity (EMP) and inducing partial epithelial-mesenchymal transition (pEMT). This "holographic patient-mirroring" platform provided unprecedented resolution for OSCC precision therapy and had been formally incorporated into the Chinese Stomatological Association Technical Guidelines (Technical guideline for establishing patient-derived oral squamous cell carcinoma organoid banks, CHSA 2024-08). Future integration of immune-competent organoids, 3D-bioprinted vasculature, and multi-omics-AI systems will accelerate personalized oncology. These innovations will accelerate clinical translation of personalized therapeutic regimens, ultimately bridging the gap between bench research and bedside application.

Key words: Oral squamous cell carcinoma, Organoid bank, Precision medicine, Drug screening, Personalized treatment

中图分类号: 

  • R739.8
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[1] 张宁,杨慧,王鹏. 类器官在癌症研究、药物筛选与精准诊疗中的应用进展[J]. 北京大学学报（医学版）, 2022, 54(5): 814-821.
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ISSN 1671-167X
CN 11-4691/R
主管单位：中华人民共和国教育部
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