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Journal of Peking University (Health Sciences) ›› 2025, Vol. 57 ›› Issue (5): 847-851. doi: 10.19723/j.issn.1671-167X.2025.05.006

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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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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

CLC Number: 

  • R739.8
1
Bray F , Laversanne M , Sung H , et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2024, 74 (3): 229- 263.
2
Han B , Zheng R , Zeng H , et al. Cancer incidence and mortality in China, 2022[J]. J Natl Cancer Cent, 2024, 4 (1): 47- 53.
3
Zhang S , Sun K , Zheng R , et al. Cancer incidence and mortality in China, 2015[J]. J Natl Cancer Cent, 2021, 1 (1): 2- 11.
4
Ma H , Shujaat S , Bila M , et al. Survival analysis of segmental mandibulectomy with immediate vascularized fibula flap reconstruction in stage Ⅳ oral squamous cell carcinoma patients[J]. J Stomatol Oral Maxillofac Surg, 2022, 123 (1): 44- 50.

doi: 10.1016/j.jormas.2020.12.003
5
Sato T , Vries RG , Snippert HJ , et al. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche[J]. Nature, 2009, 459 (7244): 262- 265.

doi: 10.1038/nature07935
6
van de Wetering M , Francies HE , Francis JM , et al. Prospective derivation of a living organoid biobank of colorectal cancer patients[J]. Cell, 2015, 161 (4): 933- 945.

doi: 10.1016/j.cell.2015.03.053
7
Sachs N , de Ligt J , Kopper O , et al. A living biobank of breast cancer organoids captures disease heterogeneity[J]. Cell, 2018, 172 (1/2): 373- 386. e10.
8
Tanaka N , Osman AA , Takahashi Y , et al. Head and neck can-cer organoids established by modification of the CTOS method can be used to predict in vivo drug sensitivity[J]. Oral Oncol, 2018, 87, 49- 57.

doi: 10.1016/j.oraloncology.2018.10.018
9
张馨元, 口腔鳞癌患者预后评估及类器官模型的初步建立[D], 北京: 北京大学, 2022.
10
Driehuis E , Kolders S , Spelier S , et al. Oral mucosal organoids as a potential platform for personalized cancer therapy[J]. Cancer discov, 2019, 9 (7): 852- 871.

doi: 10.1158/2159-8290.CD-18-1522
11
Driehuis E , Kretzschmar K , Clevers H . Establishment of patient-derived cancer organoids for drug-screening applications[J]. Nat Protoc, 2020, 15 (10): 3380- 3409.

doi: 10.1038/s41596-020-0379-4
12
王鹿鸣, 谢尚. 肿瘤类器官模型在头颈部鳞癌中的研究进展[J]. 临床口腔医学杂志, 2021, 37 (7): 440- 443.
13
Zhang XY , Sui Y , Shan XF , et al. Construction of oral squamous cell carcinoma organoids in vitro 3D-culture for drug screening[J]. Oral Dis, 2025, 31 (1): 99- 109.

doi: 10.1111/odi.15044
14
谢尚, 蔡志刚, 单小峰, 等. 一种口腔鳞癌类器官库的构建方法: CN202311378598.3[P], 2024-06-04.
15
Millen R , de Kort WWB , Koomen M , et al. Patient-derived head and neck cancer organoids allow treatment stratification and serve as a tool for biomarker validation and identification[J]. Med, 2023, 4 (5): 290. e12- 310. e12.
16
Huang X , Zhang S , Tang J , et al. A self-propagating c-met-SOX2 axis drives cancer-derived IgG signaling that promotes lung cancer cell stemness[J]. Cancer Res, 2023, 83 (11): 1866- 1882.

doi: 10.1158/0008-5472.CAN-22-2733
17
Yang X , Wang G , You J , et al. High expression of cancer-IgG is associated with poor prognosis and radioresistance via PI3K/AKT/DNA-PKcs pathway regulation in lung adenocarcinoma[J]. Front Oncol, 2021, 11, 675397.

doi: 10.3389/fonc.2021.675397
18
王鹿鸣. 癌源性免疫球蛋白G参与头颈鳞癌化疗耐药的作用及机制研究[D], 北京: 北京大学, 2025.
19
Zhao H , Jiang E , Shang Z . 3D co-culture of cancer-associated fibroblast with oral cancer organoids[J]. J Dent Res, 2021, 100 (2): 201- 208.

doi: 10.1177/0022034520956614
20
Chen X , Li R , Zhao H , et al. Phenotype transition of fibroblasts incorporated into patient-derived oral carcinoma organoids[J]. Oral Dis, 2023, 29 (3): 913- 922.

doi: 10.1111/odi.14071
21
Zhao H , Hu CY , Chen WM , et al. Lactate promotes cancer stem-like property of oral sequamous cell carcinoma[J]. Curr Med Sci, 2019, 39 (3): 403- 409.

doi: 10.1007/s11596-019-2050-2
22
Moorman A , Benitez EK , Cambulli F , et al. Progressive plasticity during colorectal cancer metastasis[J]. Nature, 2025, 637 (8047): 947- 954.

doi: 10.1038/s41586-024-08150-0
23
Xiong L , Xu Y , Gao Z , et al. A patient-derived organoid model captures fetal-like plasticity in colorectal cancer[J]. Cell Res, 2025,
24
Feng QS , Shan XF , Yau V , et al. Facilitation of tumor stroma-targeted therapy: Model difficulty and co-culture organoid method[J]. Pharmaceuticals (Basel), 2025, 18 (1): 62.

doi: 10.3390/ph18010062
25
Liao LZ, Feng QS, Shan XF, et al. Advances in biomanufacturing and medical applications of three-dimensional-printed organoids: A review[J]. IJB, 2025, 6 (2025-06-10)[2025-07-15]. https://accscience.com/journal/IJB/articles/online_first/5055.
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