北京大学学报（医学版）2025，Vol.57Issue(5)：847-851,5.DOI:10.19723/j.issn.1671-167X.2025.05.006
口腔鳞癌类器官库的构建及应用
Construction and application of oral squamous cell carcinoma organoid bank
摘要
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 squa-mous cell carcinoma organoid bank,ZL202311378598.3).Through groundbreaking optimization of cul-ture media,enzymatic digestion kinetics,and stepwise cryopreservation,we achieved a biobanking suc-cess 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 as-says;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 transi-tion(pEMT).This"holographic patient-mirroring"platform provided unprecedented resolution for OSCC precision therapy and had been formally incorporated into the Chinese Stomatological Association Techni-cal Guidelines(Technical guideline for establishing patient-derived oral squamous cell carcinoma or-ganoid banks,CHSA 2024-08).Future integration of immune-competent organoids,3D-bioprinted vas-culature,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.关键词
口腔鳞癌/类器官库/精准医疗/药物筛选/个体化治疗Key words
Oral squamous cell carcinoma/Organoid bank/Precision medicine/Drug screening/Personalized treatment分类
医药卫生引用本文复制引用
谢尚,王鹿鸣,张馨元,冯秋实,夏洋洋,戴姿薇,单小峰,蔡志刚..口腔鳞癌类器官库的构建及应用[J].北京大学学报（医学版）,2025,57(5):847-851,5.基金项目
国家重点研发计划(2022YFC2504200)、国家自然科学基金(82373434、82002878)Supported by the National Key Research & Development Program of China(2022YFC2504200),and the National Natural Science Foundation of China(82373434,82002878) （2022YFC2504200）
