Department of General Surgery of Ruijin Hospital, Shanghai Institute of Digestive Surgery, Shanghai Key Laboratory for Gastric Neoplasms, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Shanghai Engineering Center for Molecular Medicine, Zhangjiang, Shanghai, 200120, China.
J Transl Med. 2024 Aug 12;22(1):754. doi: 10.1186/s12967-024-05512-0.
Organoids are approved by the US FDA as an alternative to animal experiments to guide drug development and for sensitivity screening. Stable organoids models of gastric cancer are desirable for personalized medicine and drug screening.
Tumor tissues from a primary cancer of the stomach and metastatic cancer of the lymph node were collected for 3D culture. By long-term culture for over 50 generations in vitro, we obtained stably growing organoid lines. We analyzed short tandem repeats (STRs) and karyotypes of cancer cells, and tumorigenesis of the organoids in nude mice, as well as multi-omics profiles of the organoids. A CCK8 method was used to determine the drugs sensitivity to fluorouracil (5-Fu), platinum and paclitaxel.
Paired organoid lines from primary cancer (SPDO1P) and metastatic lymph node (SPDO1LM) were established with unique STRs and karyotypes. The organoid lines resulted in tumorigenesis in vivo and had clear genetic profiles. Compared to SPDO1P from primary cancer, upregulated genes of SPDO1LM from the metastatic lymph node were enriched in pathways of epithelial-mesenchymal transition and angiogenesis with stronger abilities of cell migration, invasion, and pro-angiogenesis. Based on drug sensitivity analysis, the SOX regimen (5-Fu plus oxaliplatin) was used for chemotherapy with an optimal clinical outcome.
The organoid lines recapitulate the drug sensitivity of the parental tissues. The paired organoid lines present a step-change toward living biobanks for further translational usage.
类器官已获得美国食品和药物管理局批准，可作为替代动物实验的方法，用于指导药物开发和敏感性筛选。胃癌稳定的类器官模型对于个性化医疗和药物筛选是理想的。
从胃原发癌和淋巴结转移癌的肿瘤组织中进行 3D 培养。通过体外长期培养超过 50 代，我们获得了稳定生长的类器官系。我们分析了癌细胞的短串联重复序列（STR）和核型，以及裸鼠中的类器官肿瘤发生情况，以及类器官的多组学图谱。使用 CCK8 法测定氟尿嘧啶（5-Fu）、铂类和紫杉醇对类器官的药物敏感性。
建立了配对的原发癌（SPDO1P）和转移性淋巴结（SPDO1LM）类器官系，具有独特的 STR 和核型。类器官系在体内导致肿瘤发生，并具有明确的遗传特征。与原发癌的 SPDO1P 相比，转移性淋巴结的 SPDO1LM 上调基因富集在上皮-间充质转化和血管生成途径中，具有更强的细胞迁移、侵袭和促血管生成能力。基于药物敏感性分析，采用 SOX 方案（5-Fu 加奥沙利铂）进行化疗，取得了最佳的临床效果。
类器官系再现了亲本组织的药物敏感性。配对的类器官系为进一步转化应用提供了活体生物库的重大进展。
