类器官被美国 FDA 批准作为动物实验的替代品，用于指导药物开发和敏感性筛查。稳定的胃癌类器官模型对于个性化医疗和药物筛选来说是理想的选择。收集原发性胃癌和转移性淋巴结癌的肿瘤组织进行3D培养。通过体外长期培养50代以上，获得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、裸鼠类器官的肿瘤发生以及类器官的多组学特征。采用CCK8方法测定药物对氟尿嘧啶(5-Fu)、铂类和紫杉醇的敏感性。建立了具有独特STR和核型的原发癌(SPDO1P)和转移性淋巴结(SPDO1LM)的配对类器官系。类器官系导致体内肿瘤发生并具有清晰的遗传图谱。与原发癌SPDO1P相比，转移淋巴结SPDO1LM上调基因在上皮间质转化和血管生成通路中富集，具有更强的细胞迁移、侵袭和促血管生成能力。根据药物敏感性分析，采用SOX方案（5-Fu加奥沙利铂）进行化疗，具有最佳的临床结果。类器官线概括了亲代组织的药物敏感性。成对的类器官系向活体生物库的进一步转化应用迈出了一步。© 2024。作者。

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.© 2024. The Author(s).