奥沙利铂
类有机物
癌症
生物标志物
医学
药品
化疗
癌症研究
个性化医疗
结直肠癌
肿瘤科
内科学
生物信息学
药理学
生物
遗传学
作者
Yi Zhao,Shangru Li,Lefan Zhu,Mingle Huang,Yubin Xie,Xinming Song,Zhihui Chen,Harry Cheuk-Hay Lau,Joseph Jao-Yiu Sung,Lixia Xu,Jun Yu,Xiaoxing Li
标识
DOI:10.1016/j.xcrm.2024.101627
摘要
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.
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