利用患者衍生的类器官进行个性化肝癌治疗
Leveraging Patient-Derived Organoids for Personalized Liver Cancer Treatment
影响因子:10.00000
分区:生物学1区 Top / 生化与分子生物学2区
发表日期:2024
作者:
Jianhua Rao, Chao Song, Yangyang Hao, Zaozao Chen, Sidu Feng, Shihui Xu, Xiaoyue Wu, Zhengfeng Xuan, Ye Fan, Wenzhu Li, Junda Li, Yong Ren, Jian Li, Feng Cheng, Zhongze Gu
摘要
原发性肝癌（PLC）是全球与癌症相关死亡的主要原因，由于可用于治疗和肿瘤异质性的选择有限，因此需要新的治疗方法。使用自我开发的2：2方法培养66个手术去除的PLC样品，器官培养的最终成功率为40.9％。已经使用综合分子测量值（例如全异常和RNA测序以及抗癌药物测试）评估了器官性能。多个类器官及其相应的肿瘤组织包含几个相同的突变，所有对共享常规TP53突变。关于拷贝数的变化和基因表达，器官之间观察到显着的相关性及其相应的亲本肿瘤组织。分子水平的比较为我们提供了对肿瘤和肿瘤一致性的评估，该一致性与药物敏感性测试结合使用，为治疗选择提供了直接的指导。最后，我们能够确定ICC患者的适当药理方案，证明了调整患者特异性药物方案的临床实用性。我们的研究提供了一种类器官培养技术，该技术可以培养保留大多数肿瘤分子特征的模型，并可用于药物敏感性测试，证明器官技术在精密医学中对肝癌治疗的广泛潜在应用。
Abstract
Primary liver cancer (PLC) is a primary cause of cancer-related death worldwide, and novel treatments are needed due to the limited options available for treatment and tumor heterogeneity. 66 surgically removed PLC samples were cultured using the self-developed 2:2 method, and the final success rate for organoid culture was 40.9%. Organoid performance has been evaluated using comprehensive molecular measurements, such as whole-exome and RNA sequencing, as well as anticancer drug testing. Multiple organoids and their corresponding tumor tissues contained several of the same mutations, with all pairs sharing conventional TP53 mutations. Regarding copy number variations and gene expression, significant correlations were observed between the organoids and their corresponding parental tumor tissues. Comparisons at the molecular level provided us with an assessment of organoid-to-tumor concordance, which, in combination with drug sensitivity testing provided direct guidance for treatment selection. Finally, we were able to determine an appropriate pharmacological regimen for a patient with ICC, demonstrating the clinical practicality in tailoring patient-specific drug regimens. Our study provides an organoid culture technology that can cultivate models that retain most of the molecular characteristics of tumors and can be used for drug sensitivity testing, demonstrating the broad potential application of organoid technology in precision medicine for liver cancer treatment.