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Abstract：
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
背景：类器官被美国FDA批准作为动物实验的替代方案，以指导药物开发和敏感性筛选。胃癌的稳定的类器官模型对于个性化医学和药物筛选是理想的。
方法:收集原发性胃癌和淋巴结转移癌的肿瘤组织进行3D培养。通过体外50代以上的长期培养，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（STRs）和核型，和裸鼠器官的肿瘤发生，以及类器官的多组学概况。CCK8方法用于测定药物对氟尿嘧啶（5-Fu）的敏感性，铂和紫杉醇。
结果：以独特的STR和核型建立了来自原发性癌（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，并具有清晰的遗传特征。与原发癌的SPDO1P相比，来自转移淋巴结的SPDO1LM的上调基因在上皮间质转化和血管生成途径中富集，细胞迁移能力更强，入侵,和促血管生成。基于药物敏感性分析，SOX方案(5-Fu+奥沙利铂)用于化疗,临床结局最佳.
结论：类器官系概括了亲本组织的药物敏感性。配对的类器官品系向活体生物库呈现阶跃变化，以进一步翻译使用。
方法:收集原发性胃癌和淋巴结转移癌的肿瘤组织进行3D培养。通过体外50代以上的长期培养，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（STRs）和核型，和裸鼠器官的肿瘤发生，以及类器官的多组学概况。CCK8方法用于测定药物对氟尿嘧啶（5-Fu）的敏感性，铂和紫杉醇。
结果：以独特的STR和核型建立了来自原发性癌（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，并具有清晰的遗传特征。与原发癌的SPDO1P相比，来自转移淋巴结的SPDO1LM的上调基因在上皮间质转化和血管生成途径中富集，细胞迁移能力更强，入侵,和促血管生成。基于药物敏感性分析，SOX方案(5-Fu+奥沙利铂)用于化疗,临床结局最佳.
结论：类器官系概括了亲本组织的药物敏感性。配对的类器官品系向活体生物库呈现阶跃变化，以进一步翻译使用。
