Abstract：
The efficacy of chemotherapy varies significantly among patients with gastric cancer (GC), and there is currently no effective strategy to predict chemotherapeutic outcomes. In this study, we successfully establish 57 GC patient-derived organoids (PDOs) from 73 patients with GC (78%). These organoids retain histological characteristics of their corresponding primary GC tissues. GC PDOs show varied responses to different chemotherapeutics. Through RNA sequencing, the upregulation of tumor suppression genes/pathways is identified in 5-fluorouracil (FU)- or oxaliplatin-sensitive organoids, whereas genes/pathways associated with proliferation and invasion are enriched in chemotherapy-resistant organoids. Gene expression biomarker panels, which could distinguish sensitive and resistant patients to 5-FU and oxaliplatin (area under the dose-response curve [AUC] >0.8), are identified. Moreover, the drug-response results in PDOs are validated in patient-derived organoids-based xenograft (PDOX) mice and are consistent with the actual clinical response in 91.7% (11/12) of patients with GC. Assessing chemosensitivity in PDOs can be utilized as a valuable tool for screening chemotherapeutic drugs in patients with GC.
摘要：
化疗的疗效在胃癌（GC）患者中差异显著，目前尚无预测化疗结果的有效策略。在这项研究中,我们成功地从73例GC患者（78％）中建立了57例GC患者来源的类器官（PDO）。这些类器官保留了其相应的原代GC组织的组织学特征。GCPDO对不同的化疗药物显示出不同的反应。通过RNA测序，在5-氟尿嘧啶（FU）-或奥沙利铂敏感的类器官中鉴定出肿瘤抑制基因/途径的上调，而与增殖和侵袭相关的基因/途径在化疗耐药的类器官中富集。基因表达生物标志物面板，可以区分对5-FU和奥沙利铂敏感和耐药的患者（剂量反应曲线下面积[AUC]>0.8），被识别。此外，PDO的药物反应结果在基于患者来源的类器官的异种移植(PDOX)小鼠中得到验证,与91.7%(11/12)的GC患者的实际临床反应一致.评估PDO中的化学敏感性可用作筛选GC患者化疗药物的有价值的工具。
